Bladder Cancer

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S1602, A Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming With Intradermal BCG Before Intravesical Therapy for BCG-Naive High-Grade Non-muscle Invasive Bladder Cancer


Condition: Stage 0 Bladder Urothelial Carcinoma, Stage 0is Bladder Urothelial Carcinoma, Stage I Bladder Urothelial Carcinoma

Intervention:

  • Biological: BCG Solution
  • Biological: BCG Tokyo-172 Strain Solution
  • Biological: BCG Tokyo-172 Strain Vaccine
  • Other: Laboratory Biomarker Analysis

Purpose: This randomized phase III trial studies Tokyo-172 strain bacillus Calmette-Guerin (BCG) solution with or without a vaccination using Tokyo-172 strain BCG to see how well it works compared with TICE BCG solution in treating patients with bladder cancer that has not spread to muscle. BCG is a non-infectious bacteria that when instilled into the bladder may stimulate the immune system to fight bladder cancer. Giving different versions of BCG with vaccine therapy may prevent bladder cancer from returning.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03091660

Sponsor: Southwest Oncology Group

Primary Outcome Measures:

  • Measure: TTHGR for Arm I compared to Arm II
  • Time Frame: Time from randomization to first high grade recurrence assessed up to 5 years
  • Safety Issue:
  • Measure: TTHGR for Arm II compared to Arm III
  • Time Frame: Time from randomization to first high grade recurrence assessed up to 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Disease free rates
  • Time Frame: At 6 months
  • Safety Issue:

Estimated Enrollment: 969

Study Start Date: February 7, 2017

Phase: Phase 3

Eligibility:

  • Age: minimum N/A maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients must have histologically proven Ta, carcinoma in situ (CIS) or T1 stage urothelial cell carcinoma of the bladder within 90 days of registration
  • Patients must have had all grossly visible papillary tumors removed within 30 days prior to registration or cystoscopy confirming no grossly visible papillary tumors within 30 days prior to registration
  • Patients with T1 disease must have cross-sectional imaging of abdomen/pelvis demonstrating no evidence of metastatic disease (magnetic resonance imaging [MRI] or computed tomography [CT] scan) within 90 days prior to registration; patients with T1 disease must have re-resection confirming =< T1 disease within 90 days prior to registration
  • Patients must have high-grade bladder cancer as defined by 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) classification
  • Patients must not have pure squamous cell carcinoma or adenocarcinoma
  • Patients' disease must not have micropapillary components
  • Patients must have no evidence of upper tract (renal pelvis or ureters) cancer confirmed by one of the following tests performed within 90 days prior to registration: CT urogram, intravenous pyelogram, magnetic resonance (MR) urogram, or retrograde pyelograms
  • Patients must not have nodal involvement or metastatic disease
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years; patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
  • Patients must have a Zubrod performance status of 0-2
  • Patients must not have received prior intravesical BCG
  • Patients must not have known history of tuberculosis
  • Patients must be PPD negative within 90 days prior to registration; PPD negativity is defined as < 10 mm diameter induration (palpable, raised hardened area) in the volar forearm at 48-72 hours following injection with standard tuberculin dose (5 units, 0.1 ml)
  • Patients must be >= 18 years of age
  • Patients must not be taking oral glucocorticoids at the time of registration
  • Patients must not be planning to receive concomitant biologic therapy, hormonal therapy, chemotherapy, surgery, or other cancer therapy while on study
  • Prestudy history and physical must be obtained within 90days prior to registration
  • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • Patients must be offered the opportunity to participate in specimen banking for future studies to include translational medicine studies

Contact:

  • Nicki Trevino
  • (210)614-8808 Ext. 1007

Locations:

  • Mayo Clinic Hospital
  • Phoenix Arizona 85054 United States
  • Mayo Clinic in Arizona
  • Scottsdale Arizona 85259 United States
  • City of Hope Comprehensive Cancer Center
  • Duarte California 91010 United States
  • Los Angeles County-USC Medical Center
  • Los Angeles California 90033 United States
  • USC / Norris Comprehensive Cancer Center
  • Los Angeles California 90033 United States
  • Kaiser Permanente-Oakland
  • Oakland California 94611 United States
  • Stanford Cancer Institute Palo Alto
  • Palo Alto California 94304 United States
  • Kaiser Permanente-Vallejo
  • Vallejo California 94589 United States
  • University of Colorado Hospital
  • Aurora Colorado 80045 United States
  • MedStar Washington Hospital Center
  • Washington District of Columbia 20010 United States
  • University of Florida Health Science Center - Gainesville
  • Gainesville Florida 32610 United States
  • Baptist MD Anderson Cancer Center
  • Jacksonville Florida 32207 United States
  • Atlanta VA Medical Center
  • Decatur Georgia 30033 United States
  • Saint Luke's Mountain States Tumor Institute
  • Boise Idaho 83712 United States
  • Saint Luke's Mountain States Tumor Institute - Fruitland
  • Fruitland Idaho 83619 United States
  • Saint Luke's Mountain States Tumor Institute - Meridian
  • Meridian Idaho 83642 United States
  • Saint Luke's Mountain States Tumor Institute - Nampa
  • Nampa Idaho 83686 United States
  • Saint Luke's Mountain States Tumor Institute-Twin Falls
  • Twin Falls Idaho 83301 United States
  • Centralia Oncology Clinic
  • Centralia Illinois 62801 United States
  • Northwestern University
  • Chicago Illinois 60611 United States
  • Carle on Vermilion
  • Danville Illinois 61832 United States
  • Cancer Care Specialists of Illinois - Decatur
  • Decatur Illinois 62526 United States
  • Decatur Memorial Hospital
  • Decatur Illinois 62526 United States
  • Carle Physician Group-Effingham
  • Effingham Illinois 62401 United States
  • Crossroads Cancer Center
  • Effingham Illinois 62401 United States
  • Carle Physician Group-Mattoon/Charleston
  • Mattoon Illinois 61938 United States
  • Southern Illinois University School of Medicine
  • Springfield Illinois 62702 United States
  • Springfield Clinic
  • Springfield Illinois 62702 United States
  • Memorial Medical Center
  • Springfield Illinois 62781 United States
  • Cancer Care Specialists of Illinois-Swansea
  • Swansea Illinois 62226 United States
  • Carle Cancer Center
  • Urbana Illinois 61801 United States
  • The Carle Foundation Hospital
  • Urbana Illinois 61801 United States
  • University of Kansas Hospital-Westwood Cancer Center
  • Westwood Kansas 66205 United States
  • East Jefferson General Hospital
  • Metairie Louisiana 70006 United States
  • Louisiana State University Health Science Center
  • New Orleans Louisiana 70112 United States
  • Ochsner Medical Center Jefferson
  • New Orleans Louisiana 70121 United States
  • Louisiana State University Health Sciences Center Shreveport
  • Shreveport Louisiana 71103 United States
  • University of Michigan Comprehensive Cancer Center
  • Ann Arbor Michigan 48109 United States
  • Henry Ford Cancer Institute?Downriver
  • Brownstown Michigan 48183 United States
  • Henry Ford Macomb Hospital-Clinton Township
  • Clinton Township Michigan 48038 United States
  • Henry Ford Medical Center-Fairlane
  • Dearborn Michigan 48126 United States
  • Henry Ford Hospital
  • Detroit Michigan 48202 United States
  • Henry Ford Medical Center-Columbus
  • Novi Michigan 48377 United States
  • Henry Ford West Bloomfield Hospital
  • West Bloomfield Michigan 48322 United States
  • Saint Francis Medical Center
  • Cape Girardeau Missouri 63703 United States
  • Benefis Healthcare- Sletten Cancer Institute
  • Great Falls Montana 59405 United States
  • Renown Regional Medical Center
  • Reno Nevada 89502 United States
  • Memorial Sloan Kettering Basking Ridge
  • Basking Ridge New Jersey 07920 United States
  • Memorial Sloan Kettering Commack
  • Commack New York 11725 United States
  • Arnot Ogden Medical Center/Falck Cancer Center
  • Elmira New York 14905 United States
  • Memorial Sloan Kettering Westchester
  • Harrison New York 10604 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States
  • University of Rochester
  • Rochester New York 14642 United States
  • UNC Lineberger Comprehensive Cancer Center
  • Chapel Hill North Carolina 27599 United States
  • Indu and Raj Soin Medical Center
  • Beavercreek Ohio 45431 United States
  • Kettering Medical Center
  • Kettering Ohio 45429 United States
  • University of Oklahoma Health Sciences Center
  • Oklahoma City Oklahoma 73104 United States
  • Mercy Hospital Oklahoma City
  • Oklahoma City Oklahoma 73120 United States
  • Bay Area Hospital
  • Coos Bay Oregon 97420 United States
  • SWOG
  • Portland Oregon 97239 United States
  • Thomas Jefferson University Hospital
  • Philadelphia Pennsylvania 19107 United States
  • Greenville Health System Cancer Institute-Laurens
  • Clinton South Carolina 29325 United States
  • Greenville Health System Cancer Institute-Easley
  • Easley South Carolina 29640 United States
  • Greenville Health System Cancer Institute-Butternut
  • Greenville South Carolina 29605 United States
  • Greenville Health System Cancer Institute-Faris
  • Greenville South Carolina 29605 United States
  • Greenville Memorial Hospital
  • Greenville South Carolina 29605 United States
  • Greenville Health System Cancer Institute-Eastside
  • Greenville South Carolina 29615 United States
  • Greenville Health System Cancer Institute-Greer
  • Greer South Carolina 29650 United States
  • Greenville Health System Cancer Institute-Seneca
  • Seneca South Carolina 29672 United States
  • Greenville Health System Cancer Institute-Spartanburg
  • Spartanburg South Carolina 29307 United States
  • UT Southwestern/Simmons Cancer Center-Dallas
  • Dallas Texas 75390 United States
  • University of Texas Medical Branch
  • Galveston Texas 77555-0565 United States
  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
  • Houston Texas 77030 United States
  • M D Anderson Cancer Center
  • Houston Texas 77030 United States
  • UTMB Cancer Center at Victory Lakes
  • League City Texas 77573 United States
  • Audie L Murphy Veterans Affairs Hospital
  • San Antonio Texas 78209 United States
  • University Hospital
  • San Antonio Texas 78229 United States
  • University of Texas Health Science Center at San Antonio
  • San Antonio Texas 78229 United States
  • Farmington Health Center
  • Farmington Utah 84025 United States
  • Huntsman Cancer Institute/University of Utah
  • Salt Lake City Utah 84112 United States
  • South Jordan Health Center
  • South Jordan Utah 84009 United States
  • Madigan Army Medical Center
  • Tacoma Washington 98431 United States
  • Marshfield Clinic-Chippewa Center
  • Chippewa Falls Wisconsin 54729 United States
  • Marshfield Clinic Cancer Center - Eau Claire
  • Eau Claire Wisconsin 54701 United States
  • Gundersen Lutheran Medical Center
  • La Crosse Wisconsin 54601 United States
  • Marshfield Clinic - Ladysmith Center
  • Ladysmith Wisconsin 54848 United States
  • Marshfield Clinic
  • Marshfield Wisconsin 54449 United States
  • Marshfield Clinic-Minocqua Center
  • Minocqua Wisconsin 54548 United States
  • Marshfield Clinic-Rice Lake Center
  • Rice Lake Wisconsin 54868 United States
  • Marshfield Clinic Stevens Point Center
  • Stevens Point Wisconsin 54482 United States
  • Marshfield Clinic-Wausau Center
  • Wausau Wisconsin 54401 United States
  • Marshfield Clinic - Weston Center
  • Weston Wisconsin 54476 United States
  • Marshfield Clinic - Wisconsin Rapids Center
  • Wisconsin Rapids Wisconsin 54494 United States

View trial on ClinicalTrials.gov


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A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination With Standard of Care Chemotherapy and Durvalumab in Combination With Tremelimumab and Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone in Patients With Unresectable Locally Advanced or Metastatic Urothelial Cancer


Condition: Unresectable Locally Advanced Urothelial Cancer, Metastatic Urothelial Cancer

Intervention:

  • Drug: Durvalumab
  • Drug: Tremelimumab
  • Drug: Cisplatin + Gemcitabine
  • Drug: Carboplatin + Gemcitabine

Purpose: This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of combining durvalumab ± tremelimumab with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra).

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03682068

Sponsor: AstraZeneca

Primary Outcome Measures:

  • Measure: Progression Free Survival (PFS)
  • Time Frame: approximately 4 years
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: approximately 4 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Overall Survival at 24 months (OS24)
  • Time Frame: 24 months
  • Safety Issue:
  • Measure: Alive and Progression Free Survival at 12 months (APF12)
  • Time Frame: 12 months
  • Safety Issue:
  • Measure: Objective Response Rate (ORR)
  • Time Frame: approximately 4 years
  • Safety Issue:
  • Measure: Duration of Response (DoR)
  • Time Frame: approximately 4 years
  • Safety Issue:
  • Measure: Disease Control Rate (DCR)
  • Time Frame: approximately 4 years
  • Safety Issue:
  • Measure: Time from randomization to second (PFS2)
  • Time Frame: approximately 4 years
  • Safety Issue:
  • Measure: To assess disease-related symptoms, physical functioning, and other Health-related quality of life
  • Time Frame: Approximately 4 years
  • Safety Issue:

Estimated Enrollment: 885

Study Start Date: September 27, 2018

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum 99 Years
  • Gender: All

Key Inclusion Criteria:

  • Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
  • Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
  • At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
  • World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
  • Adequate organ and marrow function as defined in the protocol
  • Life expectancy ≥12 weeks in the opinion of the investigator
  • Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

Key Exclusion Criteria:

  • Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
  • No severe concomitant condition that requires immunosuppression medication
  • Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Patients who may be eligible for or are being considered for radical resection during the course of the study.
  • Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

Contact:

  • AstraZeneca Clinical Study Information Center
  • 1-877-240-9479

Locations:

  • Research Site
  • Birmingham Alabama 35294 United States
  • Research Site
  • Bakersfield California 93309 United States
  • Research Site
  • Fountain Valley California 92708 United States
  • Research Site
  • Fullerton California 92835 United States
  • Research Site
  • Los Angeles California 90095 United States
  • Research Site
  • Salinas California 93901 United States
  • Research Site
  • Santa Barbara California 93105 United States
  • Research Site
  • Santa Maria California 93454 United States
  • Research Site
  • Truckee California 96161 United States
  • Research Site
  • New Haven Connecticut 06520 United States
  • Research Site
  • Orlando Florida 32806 United States
  • Research Site
  • Chicago Illinois 60611 United States
  • Research Site
  • Fort Wayne Indiana 46808 United States
  • Research Site
  • Kansas City Kansas 66160 United States
  • Research Site
  • Louisville Kentucky 40202 United States
  • Research Site
  • New Orleans Louisiana 70112 United States
  • Research Site
  • Bozeman Montana 59718 United States
  • Research Site
  • Livingston New Jersey 07039 United States
  • Research Site
  • Neptune New Jersey 07753 United States
  • Research Site
  • Bronx New York 10467 United States
  • Research Site
  • Lake Success New York 11042 United States
  • Research Site
  • New York New York 10029 United States
  • Research Site
  • New York New York 10065 United States
  • Research Site
  • Rochester New York 14642 United States
  • Research Site
  • Germantown Tennessee 38138 United States
  • Research Site
  • Fort Worth Texas 76104 United States
  • Research Site
  • Box Hill 3128 Australia
  • Research Site
  • Elizabeth Vale 5112 Australia
  • Research Site
  • Kogarah 2217 Australia
  • Research Site
  • Macquarie University 2109 Australia
  • Research Site
  • Murdoch 6150 Australia
  • Research Site
  • Orange 2800 Australia
  • Research Site
  • South Brisbane 4101 Australia
  • Research Site
  • St Albans 3021 Australia
  • Research Site
  • Curitiba 80810-050 Brazil
  • Research Site
  • Fortaleza 60810-180 Brazil
  • Research Site
  • Porto Alegre 90020-090 Brazil
  • Research Site
  • Porto Alegre 90610-000 Brazil
  • Research Site
  • Porto Alegre 91350-200 Brazil
  • Research Site
  • Ribeirão Preto 14048-900 Brazil
  • Research Site
  • Rio de Janeiro 20231-050 Brazil
  • Research Site
  • Rio de Janeiro 22793-080 Brazil
  • Research Site
  • Salvador 41950-640 Brazil
  • Research Site
  • Sao Paulo 01327-001 Brazil
  • Research Site
  • São José do Rio Preto 15090-000 Brazil
  • Research Site
  • São Paulo 01246-000 Brazil
  • Research Site
  • Burgas 8000 Bulgaria
  • Research Site
  • Pleven 5800 Bulgaria
  • Research Site
  • Plovdiv 4000 Bulgaria
  • Research Site
  • Sofia 1303 Bulgaria
  • Research Site
  • Sofia 1431 Bulgaria
  • Research Site
  • Sofia 1797 Bulgaria
  • Research Site
  • Varna Bulgaria
  • Research Site
  • Calgary Alberta T2N 4N2 Canada
  • Research Site
  • Edmonton Alberta T6G 1Z2 Canada
  • Research Site
  • Vancouver British Columbia V5Z 4E6 Canada
  • Research Site
  • Hamilton Ontario L8V 5C2 Canada
  • Research Site
  • Ottawa Ontario K1H 8L6 Canada
  • Research Site
  • Toronto Ontario M5G 2M9 Canada
  • Research Site
  • Montreal Quebec H3T 1E2 Canada
  • Research Site
  • Brno 656 91 Czechia
  • Research Site
  • Hradec Kralove 500 05 Czechia
  • Research Site
  • Olomouc 779 00 Czechia
  • Research Site
  • Ostrava 708 52 Czechia
  • Research Site
  • Praha 2 128 08 Czechia
  • Research Site
  • Praha 140 59 Czechia
  • Research Site
  • Praha 180 81 Czechia
  • Research Site
  • Budapest 1062 Hungary
  • Research Site
  • Budapest 1122 Hungary
  • Research Site
  • Budapest 1145 Hungary
  • Research Site
  • Debrecen 4032 Hungary
  • Research Site
  • Györ 9024 Hungary
  • Research Site
  • Kecskemét 6000 Hungary
  • Research Site
  • Szolnok 5004 Hungary
  • Research Site
  • Haifa 31096 Israel
  • Research Site
  • Jerusalem 91120 Israel
  • Research Site
  • Kfar Saba 95847 Israel
  • Research Site
  • Petach-Tikva 4941492 Israel
  • Research Site
  • Ramat Gan 52621 Israel
  • Research Site
  • Milano 20133 Italy
  • Research Site
  • Napoli 80131 Italy
  • Research Site
  • Orbassano 10043 Italy
  • Research Site
  • Parma 43100 Italy
  • Research Site
  • Pavia 27100 Italy
  • Research Site
  • San Giovanni Rotondo 71013 Italy
  • Research Site
  • Terni 05100 Italy
  • Research Site
  • Bunkyo-ku 113-8603 Japan
  • Research Site
  • Hirosaki-shi 036-8563 Japan
  • Research Site
  • Kanazawa-shi 920-8641 Japan
  • Research Site
  • Kita-gun 761-0793 Japan
  • Research Site
  • Koshigaya-shi 343-8555 Japan
  • Research Site
  • Koto-ku 135-8550 Japan
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  • Kyoto-shi 606-8507 Japan
  • Research Site
  • Miyazaki-city 889-1692 Japan
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  • Nagasaki-shi 852-8501 Japan
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  • Nagoya-shi 467-0001 Japan
  • Research Site
  • Niigata-shi 951-8520 Japan
  • Research Site
  • Osaka-shi 541-8567 Japan
  • Research Site
  • Osaka-shi 545-0051 Japan
  • Research Site
  • Osakasayama-shi 589-8511 Japan
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  • Shinjuku-ku 160-8582 Japan
  • Research Site
  • Suita-shi 565-0871 Japan
  • Research Site
  • Toyama-shi 930-0194 Japan
  • Research Site
  • Tsukuba-shi 305-8576 Japan
  • Research Site
  • Yokohama-shi 232-0024 Japan
  • Research Site
  • Goyang-si 10408 Korea, Republic of
  • Research Site
  • Incheon 21565 Korea, Republic of
  • Research Site
  • Seoul 02841 Korea, Republic of
  • Research Site
  • Seoul 03722 Korea, Republic of
  • Research Site
  • Seoul 05505 Korea, Republic of
  • Research Site
  • Seoul 06351 Korea, Republic of
  • Research Site
  • Suwon-si 442-723 Korea, Republic of
  • Research Site
  • Bacolod 6100 Philippines
  • Research Site
  • Baguio City 2600 Philippines
  • Research Site
  • Cebu 6000 Philippines
  • Research Site
  • Davao City 8000 Philippines
  • Research Site
  • Makati 1229 Philippines
  • Research Site
  • Manila Philippines
  • Research Site
  • Quezon City 1104 Philippines
  • Research Site
  • Bialystok 15-027 Poland
  • Research Site
  • Gdańsk 80-952 Poland
  • Research Site
  • Grudziądz 86-300 Poland
  • Research Site
  • Koszalin 75-581 Poland
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  • Lublin 20-090 Poland
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  • Warszawa 02-616 Poland
  • Research Site
  • Warszawa 02-781 Poland
  • Research Site
  • Wroclaw 53-413 Poland
  • Research Site
  • Łódź 93-509 Poland
  • Research Site
  • Ivanovo 153040 Russian Federation
  • Research Site
  • Krasnoyarsk 660133 Russian Federation
  • Research Site
  • Moscow 105229 Russian Federation
  • Research Site
  • Moscow 115280 Russian Federation
  • Research Site
  • Moscow 125284 Russian Federation
  • Research Site
  • Moscow 125367 Russian Federation
  • Research Site
  • Nizhny Novgorod 603006 Russian Federation
  • Research Site
  • Omsk 644013 Russian Federation
  • Research Site
  • Rostov-on-Don 344037 Russian Federation
  • Research Site
  • Saint-Petersburg 195067 Russian Federation
  • Research Site
  • St. Petersburg 199178 Russian Federation
  • Research Site
  • St.-Petersburg, 198205 Russian Federation
  • Research Site
  • Vologda 160012 Russian Federation
  • Research Site
  • Barcelona 08908 Spain
  • Research Site
  • Barcelona 8003 Spain
  • Research Site
  • Barcelona 8035 Spain
  • Research Site
  • Lugo 27003 Spain
  • Research Site
  • Madrid 28007 Spain
  • Research Site
  • Madrid 28034 Spain
  • Research Site
  • Madrid 28040 Spain
  • Research Site
  • Malaga 29010 Spain
  • Research Site
  • Santander 39008 Spain
  • Research Site
  • Sevilla 41013 Spain
  • Research Site
  • Taichung 404 Taiwan
  • Research Site
  • Taichung 40705 Taiwan
  • Research Site
  • Tainan 704 Taiwan
  • Research Site
  • Taipei City 10050 Taiwan
  • Research Site
  • Taipei 11217 Taiwan
  • Research Site
  • Bangkok 10300 Thailand
  • Research Site
  • Bangkok 10400 Thailand
  • Research Site
  • Chom Thon 50200 Thailand
  • Research Site
  • Adana 1260 Turkey
  • Research Site
  • Adapazari 54290 Turkey
  • Research Site
  • Ankara 06590 Turkey
  • Research Site
  • Edirne 22030 Turkey
  • Research Site
  • Istanbul 34030 Turkey
  • Research Site
  • Izmir Turkey
  • Research Site
  • Ha Noi 100000 Vietnam
  • Research Site
  • Hanoi 100000 Vietnam
  • Research Site
  • Ho Chi Minh city Vietnam
  • Research Site
  • Ho Chi Minh 700000 Vietnam

View trial on ClinicalTrials.gov


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Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer After Failure of Platinum-Based Regimen or Anti-PD-1/ PD-L1 Based Immunotherapy


Condition: Urothelial Carcinoma

Intervention:

  • Drug: Sacituzumab govitecan

Purpose: This is an international, multi-center, open-label, phase II study in patients with metastatic urothelial cancer after failure of platinum-based regimen or anti-PD-1 /PD-L1 based immunotherapy. Approximately 140 patients are anticipated to be enrolled across approximately 50 sites from North America and Europe.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03547973

Sponsor: Immunomedics, Inc.

Primary Outcome Measures:

  • Measure: Overall Response Rate (ORR)
  • Time Frame: 2 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Duration of Response (DOR)
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Progression-Free Survival (PFS)
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: 2 years
  • Safety Issue:

Estimated Enrollment: 140

Study Start Date: August 31, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients with histologically confirmed urothelial cancer.
  • ECOG Performance status score of 0 or 1.
  • Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin): 1. Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease; 2. Or received adjuvant platinum-containing therapy following cystectomy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
  • Cohort 1: In addition to above criterion, must have had progression or recurrence of urothelial cancer following receipt of an anti-PD-1 /PD-L1 therapy.
  • Cohort 2: Were ineligible for cisplatin-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease after an anti-PD-1/PD-L1 therapy.
  • Adequate hematology, chemistry renal and hepatic function and coagulation values without ongoing transfusional.
  • Subjects must have a 3-month life expectancy.
  • Have measurable disease by CT or MRI as per RECIST 1.1 criteria.

Exclusion Criteria:

  • Women who are pregnant or lactating.
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of trial treatment.
  • Has a diagnosis of immunodeficiency.
  • Has had prior irinotecan therapy.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Requires concomitant medication interfering with ABCA1 transporter or UGT1A1
  • Subjects with Gilbert's disease.
  • Has a known additional malignancy that is progressing or requires active treatment.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has active cardiac disease, Myocardial infarction or unstable angina pectoris within 6 months of the first date of study therapy.
  • Has active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) and subjects with a history of bowel obstruction.
  • Has prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of enrollment.
  • Must be at least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids ≤ 20 mg prednisone or equivalent daily are permitted provided the dose is stable for 4 weeks).
  • Has an active infection requiring systemic therapy.
  • Has a known history of Human Immunodeficiency Virus, Hepatitis B or Hepatitis C
  • Has other concurrent medical or psychiatric conditions

Contact:

  • Allison gladden
  • 973-605-8200

Locations:

  • American Institute of Research
  • Tucson Arizona 85712 United States
  • American Institute of Research
  • Whittier California 90603 United States
  • Smilow Cancer Hospital at Yale-New Haven
  • New Haven Connecticut 06510 United States
  • Norton Cancer Institute
  • Louisville Kentucky 40241 United States
  • University of Michigan Comprehensive Medical Center
  • Ann Arbor Michigan 48109 United States
  • University of Mississippi Medical Center
  • Jackson Mississippi 38677 United States
  • Urology Cancer Center
  • Omaha Nebraska 68130 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89134 United States
  • New Mexico Oncology Hematology Consultants/Precision Cancer Research
  • Albuquerque New Mexico 87109 United States
  • Roswell Park Cancer Institute
  • Buffalo New York 14203 United States
  • New York University Langone Medical
  • New York New York 10016 United States
  • Weill Cornell Medicine
  • New York New York 10021 United States
  • Stony Brook Medicine Cancer Care
  • Stony Brook New York 11794 United States
  • Vanderbilt-Ingram Cancer Center
  • Nashville Tennessee 37232 United States
  • Renovatio Clinical Consultants
  • Houston Texas 77056 United States
  • Huntsman Cancer Hospital
  • Salt Lake City Utah 84112 United States
  • Seattle Cancer Care Alliance at South Lake Union
  • Seattle Washington 98109 United States

View trial on ClinicalTrials.gov


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A Phase 3, Randomized, Comparator-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in Participants With High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) That is Persistent or Recurrent Following BCG Induction (KEYNOTE-676)


Condition: High-risk Non-muscle Invasive Bladder Cancer

Intervention:

  • Biological: Pembrolizumab
  • Biological: BCG

Purpose: This study is designed to assess the antitumor efficacy and safety of pembrolizumab in combination with BCG, compared to BCG monotherapy, in participants with HR NMIBC that is persistent or recurrent following adequate BCG induction. The primary hypothesis is that the combination of pembrolizumab plus BCG has a superior complete response rate (CRR) as assessed by central pathology review compared to BCG in participants with carcinoma in situ (CIS).

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03711032

Sponsor: Merck Sharp & Dohme Corp.

Primary Outcome Measures:

  • Measure: Complete Response Rate (CRR) by Blinded Independent Central Review (BICR)
  • Time Frame: Up to ~3.5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Event-Free Survival (EFS)
  • Time Frame: Up to ~5 years
  • Safety Issue:
  • Measure: Recurrence-Free Survival (RFS)
  • Time Frame: Up to ~5 years
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: Up to ~5 years
  • Safety Issue:
  • Measure: Disease Specific Survival (DSS)
  • Time Frame: Up to ~5 years
  • Safety Issue:
  • Measure: Time to Cystectomy
  • Time Frame: Up to ~5 years
  • Safety Issue:
  • Measure: 12-Month EFS Rate
  • Time Frame: 12 months after EFS (up to ~5 years)
  • Safety Issue:
  • Measure: Duration of Response (DOR)
  • Time Frame: Up to ~5 years
  • Safety Issue:
  • Measure: 12-Month DOR Rate
  • Time Frame: 12 months after CR (up to ~4.5 years)
  • Safety Issue:
  • Measure: Time to True Deterioration (TTD) in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30)
  • Time Frame: time of last PRO assessment (up to ~2 years)
  • Safety Issue:
  • Measure: Percentage of Participants Experiencing Adverse Events (AEs)
  • Time Frame: Up to ~5 years
  • Safety Issue:
  • Measure: Percentage of Participants Discontinuing Study Drug Due to AEs
  • Time Frame: Up to ~5 years
  • Safety Issue:
  • Measure: Change From Baseline in EORTC-QLQ-C30 Global Health Status (Item 29) Scale Score
  • Time Frame: Baseline, time of last PRO assessment (up to ~2 years)
  • Safety Issue:
  • Measure: Change from Baseline in EORTC-QLQ-C30 Quality of Life (Item 30) Scale Score
  • Time Frame: Baseline, time of last PRO assessment (up to ~2 years)
  • Safety Issue:
  • Measure: Change from Baseline in EORTC-QLQ-C30 Score
  • Time Frame: Baseline, time of last PRO assessment (up to ~2 years)
  • Safety Issue:
  • Measure: Change from Baseline in EORTC QLQ-Non-Muscle Invasive Bladder Cancer Module 24 (NMIBC24) Score
  • Time Frame: Baseline, time of last PRO assessment (up to ~2 years)
  • Safety Issue:
  • Measure: Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Index Score
  • Time Frame: Baseline, time of last PRO assessment (up to ~2 years)
  • Safety Issue:
  • Measure: Change from Baseline in EuroQoL Visual Analogue Score (EQ VAS)
  • Time Frame: Baseline, time of last PRO assessment (up to ~2 years)
  • Safety Issue:

Estimated Enrollment: 550

Study Start Date: December 24, 2018

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Has histologically-confirmed diagnosis of non-muscle invasive (T1, high grade Ta and/or CIS) transitional cell carcinoma (TCC) of the bladder
  • Has been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC
  • Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC
  • Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to remove all resectable disease
  • Has provided tissue for biomarker analysis
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Has adequate organ function
  • Male participants must agree to use approved contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
  • Female participants who are not pregnant, not breastfeeding, and either not a woman of child bearing potential (WOCBP) or are a WOCBP who agrees to use approved contraception during the treatment period and for at least 120 days after the last dose of study treatment

Exclusion Criteria:

  • Has persistent T1 disease following an induction course of BCG
  • Has muscle invasive (i.e., T2, T3, T4), locally advanced non-resectable or metastatic UC
  • Has concurrent extra-vesical (i.e., urethra, ureter, renal pelvis) non-muscle invasive TCC of the urothelium, concurrent upper tract involvement, or invasive prostatic TCC including T1 or greater disease, or ductal invasion
  • WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization
  • Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment
  • Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has evidence of active tuberculosis
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment

Contact:

  • Toll Free Number
  • 1-888-577-8839

Locations:

  • Alaska Urological Institute dba Alaska Clinical Research Center ( Site 1083)
  • Anchorage Alaska 99503 United States
  • Skyline Urology ( Site 1065)
  • Torrance California 90905 United States
  • Woodlands Medical Specialists, PA ( Site 8002)
  • Pensacola Florida 32503 United States
  • Wichita Urology Group ( Site 1086)
  • Wichita Kansas 67226 United States
  • Michigan Institute of Urology ( Site 1077)
  • Troy Michigan 48084 United States
  • Coastal Urology Associates ( Site 1055)
  • Brick New Jersey 08724 United States
  • Rutgers Cancer Institute of New Jersey ( Site 1059)
  • New Brunswick New Jersey 08903 United States
  • Associated Medical Professionals of NY ( Site 1078)
  • Syracuse New York 13210 United States
  • MidLantic Urology ( Site 1071)
  • Bala-Cynwyd Pennsylvania 19004 United States
  • Carolina Urologic Research Center ( Site 1085)
  • Myrtle Beach South Carolina 29572 United States
  • Urology Associates [Nashville, TN] ( Site 1072)
  • Nashville Tennessee 37209 United States
  • Texas Oncology - Fort Worth Cancer Center ( Site 8003)
  • Fort Worth Texas 76104 United States
  • Texas Oncology-Plano West ( Site 8001)
  • Plano Texas 75093 United States
  • Urology of Virginia ( Site 1070)
  • Virginia Beach Virginia 23462 United States
  • Sydney Adventist Hospital ( Site 0001)
  • Wahroonga New South Wales (Australia) 2076 Australia
  • Nothern Cancer Institute ( Site 0003)
  • St Leonards New South Wales 2065 Australia
  • Univ. Klinik f. Urologie Innsbruck ( Site 0051)
  • Innsbruck 6020 Austria
  • Ordensklinikum Linz GmbH Elisabethinen ( Site 0052)
  • Linz 4020 Austria
  • AZ Maria Middelares Gent ( Site 0102)
  • Gent 9000 Belgium
  • CHU UCL Namur Site de Godinne ( Site 0103)
  • Yvoir 5530 Belgium
  • CIUSSS du Saguenay-Lac-St-Jean ( Site 0164)
  • Chicoutimi Quebec G7H 5H6 Canada
  • CHU de Quebec - Hotel-Dieu de Quebec ( Site 0151)
  • Quebec G1R 2J6 Canada
  • Tampere University Hospital [Tampere Finland] ( Site 0201)
  • Tampere 33520 Finland
  • Korea University Anam Hospital ( Site 0801)
  • Seoul 02841 Korea, Republic of
  • Seoul National University Hospital ( Site 0802)
  • Seoul 03080 Korea, Republic of
  • Asan Medical Center ( Site 0804)
  • Seoul 05505 Korea, Republic of
  • Samsung Medical Center ( Site 0803)
  • Seoul 06351 Korea, Republic of
  • University Malaya Medical Centre ( Site 1180)
  • Kuala Lumpur 59100 Malaysia
  • Akershus University Hospital ( Site 0553)
  • Lorenskog 1478 Norway
  • Stavanger universitetssykehus ( Site 0555)
  • Stavanger 4011 Norway
  • LIFTMED ( Site 0652)
  • Rybnik 44-200 Poland
  • Urologica Praktyka Lekarska Adam Marcheluk ( Site 0654)
  • Siedlce 08-110 Poland
  • Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku ( Site 0655)
  • Slupsk 76-200 Poland
  • Hospital CUF Descobertas ( Site 0706)
  • Lisboa 1998-018 Portugal
  • Hospital Universitario Quiron Madrid ( Site 0862)
  • Pozuelo de Alarcon Madrid 28223 Spain
  • Clinica Universitaria de Navarra ( Site 0863)
  • Pamplona Navarra 31008 Spain
  • Hospital Universitario Lucus Augusti ( Site 0852)
  • Lugo 27003 Spain
  • Hospital Universitario Gregorio Maranon ( Site 0854)
  • Madrid 28007 Spain
  • Clinica Universitaria Navarra - Madrid ( Site 0860)
  • Madrid 28027 Spain
  • MD Anderson Cancer Center Madrid ( Site 0859)
  • Madrid 28033 Spain
  • Hospital Universitario Ramon y Cajal ( Site 0857)
  • Madrid 28034 Spain
  • Hospital La Fe de Valencia ( Site 0855)
  • Valencia 46026 Spain
  • Eskisehir Osmangazi Universitesi Hastanesi ( Site 0953)
  • Eskisehir 26480 Turkey
  • Dokuz Eylul Universitesi ( Site 0959)
  • Izmir 35340 Turkey
  • Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0961)
  • Konya 42000 Turkey
  • Raigmore Hospital ( Site 1006)
  • Inverness Highland IV2 3UJ United Kingdom

View trial on ClinicalTrials.gov


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Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma: A Feasibility Phase II Randomized Clinical Trial ("URANUS")"


Condition: Upper Tract Urothelial Carcinoma

Intervention:

  • Procedure: RNU
  • Drug: Gemcitabine/Cisplatin
  • Drug: M-VAC Protocol

Purpose: The aim of this study is to explore feasibility of Upper Tract Urothelial Carcinoma (UTUC) treatments based in real world data in various European countries. The study will allow to gain insight in the true proportion of patients that fit to receive complete cisplatin-based neo-adjuvant or adjuvant chemotherapy, and the proportion and clinical outcome of patients with poor prognostic factors (PS and renal function) who receive only standard treatment (Radical nephroureterectomy (RNU)). This comparison will be made using a uniform diagnostic and treatment protocol.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02969083

Sponsor: The European Uro-Oncology Group

Primary Outcome Measures:

  • Measure: Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy
  • Time Frame: 6 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Disease Free Survival (DFS)
  • Time Frame: 1-2 years
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: 1-2 years
  • Safety Issue:
  • Measure: Cancer-Specific Survival (CSS)
  • Time Frame: 1-2 years
  • Safety Issue:

Estimated Enrollment: 210

Study Start Date: May 28, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Written informed consent
  • Age > 18 years
  • Histological and radiological defined UTUC: Histologically-confirmed diagnosis of predominantly urothelial carcinoma of the upper urinary tract Patients with UTUC cT2-pT4 cN0-N1 M0 (TNM classification)
  • Women with negative serum pregnancy test within 14 days of first dose of study treatment and agreement to use effective contraception
  • Patients without bladder cancer or with concomitant non muscle invasive bladder cancer
  • Adequate organ system function defined as follows: Hematologic: Absolute neutrophil count (ANC) 1.5 X 109/L; Haemoglobin 5.6 mmol/L (9.02g/dL); Platelets 100 X 109/L; Prothrombin time (PT) or international normalized ratio (INR)b 1.2 X ULN; Activated partial thromboplastin time (aPTT)1.2 X Upper limit of normal (ULN). Hepatic: Total bilirubin 1.5 X ULN; Alanine amino transferase (ALT) and Aspartate aminotransferase (AST) 2.5 X ULN. Renal: GRF 55 ml/min: Electrolytes: potassium, magnesium and calcium: within normal limits.
  • CT scan of the chest, abdomen and pelvis and Bone scan without evidence of distant metastasis Exclusion Criteria:
  • Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma.
  • History of cardiovascular conditions within the past 6 months.
  • Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an

Exclusion Criteria:

  • Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma.
  • History of cardiovascular conditions within the past 6 months.
  • Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an exclusion criteria but requires anticoagulation treatment.
  • Any major contraindication to a surgical procedure.
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • Active infection contraindicating chemotherapy
  • Concomitant diseases that are a formal exclusion to platinum-based chemotherapy (deafness, grade II neuropathy).
  • Other active neoplasms. Patients with in situ cervical carcinoma, non-melanoma skin cancer or prostate cancer T1 Gleason <7, Prostate specific antigen (PSA)
  • Concomitant muscle invasive bladder cancer
  • Patients who have been or still are on methotrexate treatment.

Contact:

  • Cristina Alvarez, MSc, PhD
  • +31(0)715264109

Location:

  • Leiden University Medical Centre
  • Leiden South Holland Netherlands

View trial on ClinicalTrials.gov


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Neoadjuvant Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing


Condition: Bladder Cancer

Intervention:

  • Drug: Nivolumab
  • Drug: Gemcitabine
  • Drug: Cisplatin

Purpose: This is a phase 2 trial seeking to define the safety and activity of gemcitabine, cisplatin, plus nivolumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer and to define the role of clinical complete response in predicting benefit in patients opting to avoid cystectomy.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03558087

Sponsor: Matthew Galsky

Primary Outcome Measures:

  • Measure: Determine the clinical complete response rate (cT0 or cTa) with gemcitabine, cisplatin, plus nivolumab
  • Time Frame: 24 months
  • Safety Issue:
  • Measure: Determine the ability of clinical complete response (cT0 or cTa) to predict benefit from treatment.
  • Time Frame: 24 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Assess Adverse Events
  • Time Frame: 24 months
  • Safety Issue:
  • Measure: Bladder intact overall survival
  • Time Frame: 24 Months
  • Safety Issue:
  • Measure: Recurrence-free survival
  • Time Frame: 24 months
  • Safety Issue:
  • Measure: Pathologic complete response rate in patients undergoing cystectomy
  • Time Frame: 24 Months
  • Safety Issue:
  • Measure: Determine the association between a prespecified panel of genomic biomarkers and benefit from treatment in patients achieving a clinical complete response.
  • Time Frame: 24 months
  • Safety Issue:

Estimated Enrollment: 63

Study Start Date: July 13, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • ECOG Performance Status of ≤ 1 within 28 days prior to registration.
  • Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder (i.e., ct2-4n0m0). candidate for cystectomy as per treating physician.
  • Demonstrate adequate organ function per listed criteria:
  • Absolute Neutrophil Count (ANC): ≥ 1.5 x 10^9/L
  • Hemoglobin (Hgb): ≥ 9 g/dL
  • Platelets: ≥ 100 x 10^9/L
  • Calculated creatinine clearance: Creatinine ≤ 1.5 or creatinine clearance ≥ 60 mL/min
  • Bilirubin: ≤ 1.5 × upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) : ≤ 3 × ULN
  • Alanine aminotransferase (ALT) : ≤ 3 × ULN
  • All subjects must have adequate archival tissue submitted prior to registration (i.e., at least 15 unstained slides or paraffin block).
  • Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception.
  • Women of childbearing potential must have a negative serum or urine pregnancy within 7 days prior to C1D1.
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.

Exclusion Criteria:

  • Prior treatment with systemic chemotherapy for muscle-invasive urothelial cancer of the bladder
  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
  • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
  • Grade ≥ 2 neuropathy (NCI CTCAE version 4).
  • Prior radiation therapy for bladder cancer
  • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Solid organ or allogeneic stem cell transplant

Contact:

  • Matthew Galsky, MD
  • 212-659-5599

Locations:

  • City of Hope
  • Duarte California 91010 United States
  • Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center
  • New York New York 10029 United States

View trial on ClinicalTrials.gov


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Evaluation of Non-Invasive Assays for the Detection of Urothelial Cancer of the Bladder and Kidney


Condition: Urothelial Cancer, Cancer, Bladder Neoplasms, Urinary Bladder Cancer

Purpose: The purpose of this study is to determine if analysis of DNA and protein material found in urine will be useful in the detection of urothelial cancer of the bladder and kidney. This analysis may be helpful to determine if how a particular cancer will act regarding remission and recurrence

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT00872495

Sponsor: Lahey Clinic

Primary Outcome Measures:

  • Measure: To evaluate the utility of emerging technologies in the detection of bladder tumor cells using non-invasive approaches utilizing voided urine samples.
  • Time Frame: Ongoing Lab analysis for study duration: final data completion date
  • Safety Issue:

Estimated Enrollment: 500

Study Start Date: September 2002

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Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients scheduled to have a nephroureterectomy, cystectomy, cytoscopy (newly diagnosed bladder cancer and those with recurrent disease in follow up)
  • Control Group: No known evidence of bladder cancer-one urine sample
  • > than 18 years of age

Exclusion Criteria:

  • < than 18 years of age

Contact:

  • Kimberly Rieger-Christ, PhD
  • 781-744-2969

Location:

  • Lahey Clinic, Inc.
  • Burlington Massachusetts 01805 United States

View trial on ClinicalTrials.gov


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A Multicenter Study of TAR-200 in Combination With Nivolumab (OPDIVO) in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy


Condition: Bladder Cancer TNM Staging Primary Tumor (T) T2, Bladder Cancer TNM Staging Primary Tumor (T) T2A, Bladder Cancer TNM Staging Primary Tumor (T) T2B, Bladder Cancer TNM Staging Primary Tumor (T) T3, Bladder Cancer TNM Staging Primary Tumor (T) T3A, Bladder Cancer TNM Staging Primary Tumor (T) T3B, Bladder Cancer TNM Staging Regional Lymph Node (N) N0, Bladder Cancer TNM Staging Regional Lymph Node (N) N1, Bladder Cancer TNM Staging Distant Metastasis (M) M0

Intervention:

  • Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200
  • Drug: Nivolumab Injection [Opdivo]

Purpose: The purpose of this study is to determine if TAR-200, an investigational drug delivery system, in combination with nivolumab is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) who are scheduled for radical cystectomy (RC) during an 84-day dosing cycle induction period comprised of four consecutive 21-day dosing cycles.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03518320

Sponsor: Taris Biomedical LLC

Primary Outcome Measures:

  • Measure: Number of participants with incidence of treatment emergent adverse events (TEAEs) over 4 consecutive 21-day dosing cycles of TAR-200 in combination with Nivolumab as assessed by CTCAE V4.0.
  • Time Frame: Study Day 0 to Study Day 180
  • Safety Issue:
  • Measure: Number of participants that do not require treatment discontinuation prior to the scheduled end date due to meeting any of the Subject Stopping Safety criteria or other drug or device related AE
  • Time Frame: Study Day 0 to Study Day 180
  • Safety Issue:

Estimated Enrollment: 25

Study Start Date: November 2018

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • 1. Histological proof of muscle-invasive urothelial carcinoma of the bladder (stage cT2-cT3b, N0-1, M0). Subjects with mixed histology are required to have documented dominant transitional cell pattern with no more than 10% squamous differentiation and 10% glandular differentiation. Micropapillary/sarcomatoid/adenocarcinoma/plasmacytoid variants are not allowed. 2. Subjects with a total tumor size of ≤2 cm following TURBT are eligible. Subjects with a tumor or tumors totaling >2 cm at screening must undergo a second debulking TURBT to reduce the tumor(s) to ≤2 cm to be eligible for treatment. 3. Adequate bone marrow, liver, and renal function, as documented by the following laboratory assessments conducted within 28 days prior to dosing:
  • Hemoglobin ≥9.0 g/dL
  • Absolute neutrophil count (ANC) ≥1,500/mm3
  • Platelet count ≥100,000/mm3
  • Total bilirubin ≤1.5x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x ULN
  • Glomerular filtration rate (GFR) ≥30 ml/min/1.73 m2 (assessed using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) 4. Willing to undergo multiple cystoscopies during the study for TAR-200 removal and post-insertion examination. 5. Deemed eligible for and willing to undergo RC by the attending urologist. 6. Subjects must refuse cisplatin-based combination chemotherapy (and understand the risk and benefits of doing so) or be deemed ineligible for cisplatin-based chemotherapy by meeting at least one of the following criteria:
  • GFR <60 mL/min/1.73 m2 (assessed using the CKD-EPI equation)
  • Common Terminology Criteria for Adverse Events (CTCAE) v4 Grade ≥2 audiometric hearing loss
  • CTCAE v4 Grade ≥2 peripheral neuropathy 7. Prior systemic chemotherapy for indications other than urothelial cell carcinoma of the bladder is permitted. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (National Cancer Institute CTCAE version 4.03) or baseline before administration of study drug. Participants with toxicities attributed to prior anti cancer therapy which are not expected to resolve and result in long lasting sequelae, such as peripheral neuropathy after platinum-based therapy or audiometric hearing loss, are permitted to enroll. 8. Written informed consent and authorization for release of personal health information obtained according to local laws. 9. Age ≥18 years at the time of consent. 10. Women of childbearing potential (WOCBP) must be willing to use a highly effective method of contraception (hormonal or intrauterine device [IUD] method of birth control with a failure rate of <1% when used consistently and correctly; or abstinence) for the duration of treatment with TAR-200 in combination with nivolumab plus 5 half-lives of study treatment, plus 30 days (duration of ovulatory cycle), for a total of 5 months post treatment completion. Note: WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements, but still must undergo pregnancy testing as described in this protocol. 11. WOCBP must have a negative pregnancy test within 24 hours prior to Study Day 0. 12. Males must be willing to use an effective method of contraception to avoid seminal transfer (double barrier method) or abstinence for the duration of treatment with TAR 200 in combination with nivolumab plus 5 half-lives of the study treatment, plus 90 days (duration of sperm turnover), for a total of 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. 13. Azoospermic males should also use double barrier contraceptive methods to avoid contamination of the non-treatment sexual partner. Exclusion Criteria: 1. Active malignancies within 3 years except for those with a negligible risk of metastasis or death treated with expected curative outcome. 2. Prior systemic chemotherapy for urothelial cell carcinoma of the bladder. 3. Prior treatment with an anti-programmed death-1 (PD-1), anti-PD-L1, anti PD L2, anti-CD137, or anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways. 4. Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis. 5. Subjects who require immunosuppressive medications such as methotrexate, tumor necrosis factor inhibitors, or systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 6. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 7. Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use, or removal of TAR 200. 8. Pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted as long as it does not interfere with placement or retention of TAR-200 in the bladder. 9. Indwelling catheters are not permitted. 10. Subjects with evidence of bladder perforation during diagnostic cystoscopy may be treated if perforation has resolved prior to dosing. 11. Bladder post-void residual volume of >500 mL. 12. History of diagnosis of neurogenic bladder requiring intermittent catheterization. 13. Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection (UTI). Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study. 14. Subjects with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus RNA or hepatitis C antibody (HCV antibody) indicating acute or chronic infection. 15. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at sites where mandated locally. 16. Uncontrolled adrenal insufficiency. 17. New York Heart Association Functional Classification of Heart Failure: Class III or IV (Appendix 1). 18. Eastern Cooperative Oncology Group (ECOG) performance status ≥2. 19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements. 20. Subjects who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation. 21. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. 22. Subjects must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before Study Day 0. 23. History of allergy or hypersensitivity to gemcitabine (or other drug excipients in TAR-200) or drugs chemically-related to gemcitabine. 24. History of allergy or hypersensitivity to the device constituent or Inserter materials. 25. History of allergy or hypersensitivity to nivolumab drug components. 26. Female subject who is pregnant (as verified by urine test at time of screening) or lactating or of childbearing potential and not using acceptable methods of contraception. 27. Difficulty providing blood samples. 28. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. 29. Use of an investigational product (IP) within 30 days or 5 half-lives, whichever is longer, preceding Study Day 0. 30. Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and sponsor approval is required.) 31. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness Other protocol defined inclusion/

Exclusion Criteria:

  1. Active malignancies within 3 years except for those with a negligible risk of metastasis or death treated with expected curative outcome.
  2. Prior systemic chemotherapy for urothelial cell carcinoma of the bladder.
  3. Prior treatment with an anti-programmed death-1 (PD-1), anti-PD-L1, anti PD L2, anti-CD137, or anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways.
  4. Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis.
  5. Subjects who require immunosuppressive medications such as methotrexate, tumor necrosis factor inhibitors, or systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  6. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  7. Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use, or removal of TAR 2
  8. Pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted as long as it does not interfere with placement or retention of TAR-200 in the bladder.
  9. Indwelling catheters are not permitted.
  10. Subjects with evidence of bladder perforation during diagnostic cystoscopy may be treated if perforation has resolved prior to dosing.
  11. Bladder post-void residual volume of >500 mL.
  12. History of diagnosis of neurogenic bladder requiring intermittent catheterization.
  13. Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection (UTI). Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study.
  14. Subjects with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus RNA or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
  15. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at sites where mandated locally.
  16. Uncontrolled adrenal insufficiency.
  17. New York Heart Association Functional Classification of Heart Failure: Class III or IV (Appendix 1).
  18. Eastern Cooperative Oncology Group (ECOG) performance status ≥
  19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
  20. Subjects who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
  21. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  22. Subjects must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before Study Day
  23. History of allergy or hypersensitivity to gemcitabine (or other drug excipients in TAR-200) or drugs chemically-related to gemcitabine.
  24. History of allergy or hypersensitivity to the device constituent or Inserter materials.
  25. History of allergy or hypersensitivity to nivolumab drug components.
  26. Female subject who is pregnant (as verified by urine test at time of screening) or lactating or of childbearing potential and not using acceptable methods of contraception.
  27. Difficulty providing blood samples.
  28. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  29. Use of an investigational product (IP) within 30 days or 5 half-lives, whichever is longer, preceding Study Day
  30. Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and sponsor approval is required.)
  31. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness Other protocol defined inclusion/exclusion criteria could apply.

Contact:

  • TARIS Biomedical LLC
  • +1-781-676-7750

Locations:

  • DuPage Medical Group
  • Hinsdale Illinois 60521 United States
  • University of Rochester Medical Center
  • Rochester New York 14642 United States
  • Duke University Medical Center
  • Durham North Carolina 27710 United States
  • The University of Oklahoma Stephenson Cancer Center
  • Oklahoma City Oklahoma 73104 United States
  • Thomas Jefferson University
  • Philadelphia Pennsylvania 19107 United States
  • Vanderbilt University Medical Center
  • Nashville Tennessee 37232 United States

View trial on ClinicalTrials.gov


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Phase II Study of Pembrolizumab (MK-3475) as First-Line Therapy for High Risk T1 Non-Muscle-Invasive Bladder Cancer


Condition: Bladder Cancer

Intervention:

  • Drug: Pembrolizumab (MK-3475)

Purpose: The purpose of this study is to find out what effects, good and/or bad, pembrolizumab has on the participant and urothelial cancer.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03504163

Sponsor: Memorial Sloan Kettering Cancer Center

Primary Outcome Measures:

  • Measure: The proportion of patients who are disease-free
  • Time Frame: 6 months
  • Safety Issue:

Estimated Enrollment: 37

Study Start Date: June 27, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Be willing and able to provide written informed consent/assent for the trial.
  • Histologically confirmed urothelial cancer by TURBT performed at MSKCC.
  • TURBT within 6 weeks of protocol entry with complete resection of all papillary lesions.
  • Patients with high risk, BCG-naïve non-muscle-invasive urothelial cancer defined as having one of the following disease states:
  • T1 on restaging biopsy, plus cis
  • Multiple (≥ 1) T1 recurrences, plus cis
  • Multifocal T1 plus cis
  • T1b, plus cis
  • T1 with lymphovascular invasion plus cis
  • Patient refusal of cystectomy and bilateral pelvic lymphadenectomy
  • No prior intravesical therapy.
  • No prior radiation therapy for bladder cancer. Prior radiation therapy for prostate cancer is allowed.
  • ECOG performance status 0 or 1.
  • Age ≥ 18 years of age
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of the study medication (reference section 9.5.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Patients must not have other invasive malignancies within the past 5 years (with the exception of non-melanoma skin cancers, localized prostate cancer, and carcinoma in situ of the cervix).
  • Required Initial Laboratory Values:
  • Absolute neutrophil count ≥ 1.5 x 10E9/L
  • Platelets ≥ 100 x 10E9/L
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin ≤ 1.5 times the upper limit of normal (x ULN)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN
  • Calculated creatinine clearance ≥ 30 using the CKD-Epi formula

Exclusion Criteria:

  • Prior treatment with systemic chemotherapy
  • Unstable angina
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction within 6 months
  • History of stroke within 6 months
  • Evidence of bleeding diathesis or coagulopathy
  • Presence of any systemic metastases (ie, nodal, visceral, or central nervous system)
  • Major surgical procedure (other than TURBT) within 28 days prior to the study
  • Pregnant (positive pregnancy test) or lactating
  • Serious, non-healing wound, ulcer, or bone fracture
  • Inability to comply with study and/or follow-up procedures
  • Prior therapy with an anti-PD-1 agent, anti-PD-L1 agent, or other inhibitory or stimulatory agent oriented towards a T-cell receptor
  • Active infection requiring systemic therapy
  • Known history of human immunodeficiency virus (HIV)
  • Known active Hepatitis B or Hepatitis C
  • Received live attenuated vaccines within 30 days prior to start of study treatment. Patients must also agree to avoid live attenuated vaccines during study treatment.
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic or immunosuppressive agents. Subjects with vitiligo, diabetes Type I, or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjøgren's syndrome will not be excluded from the study.

Contact:

  • Dean Bajorin, MD
  • 646-422-4333

Location:

  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States

View trial on ClinicalTrials.gov


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An Open-Label, Multi-Center Trial of INO-5401 + INO-9012 in Combination With Atezolizumab in Subjects With Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma


Condition: Urothelial Carcinoma

Intervention:

  • Biological: INO-5401
  • Biological: INO-9012
  • Drug: Atezolizumab
  • Device: CELLECTRA™ 2000

Purpose: This is a Phase I/IIA, open-label, multi-center trial to evaluate the safety, immunogenicity and preliminary clinical efficacy of INO-5401 + INO-9012 delivered by intramuscular (IM) injection followed by electroporation (EP), in combination with atezolizumab in participants with locally advanced unresectable or metastatic/recurrent Urothelial Carcinoma (UCa). The trial population is divided into two cohorts: Cohort A: Participants with locally advanced unresectable or metastatic/recurrent UCa, who have confirmed disease progression during or following treatment with anti-Programmed Death receptor-1/Programmed Death receptor Ligand-1 (anti-PD-1/PD-L1) therapy; Cohort B: Participants with locally advanced unresectable or metastatic/recurrent UCa, who are treatment naïve and ineligible for cisplatin-based chemotherapy. A safety run-in will be performed with up to six participants (safety analysis participants) from cohort A.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03502785

Sponsor: Inovio Pharmaceuticals

Primary Outcome Measures:

  • Measure: Number of Adverse Events
  • Time Frame: From baseline up to 90 days after last dose of study medication (up to approximately 2 years and 3 months)
  • Safety Issue:
  • Measure: Antigen-Specific Cellular Immune Response
  • Time Frame: At baseline, Weeks 3, 6, 9, 12 and every 12 weeks thereafter up to end of study (up to approximately 2 years)
  • Safety Issue:
  • Measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator Review in Cohort A
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: ORR by RECIST version 1.1 by Investigator Review in Cohort B
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: ORR by Immune RECIST (iRECIST)
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: Duration of Response (DoR)
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: Progression Free Survival (PFS) as Assessed by RECIST version 1.1 and iRECIST
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: : From Baseline to the time of death from any cause (up to approximately 2 years)
  • Safety Issue:

Estimated Enrollment: 85

Study Start Date: May 24, 2018

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Sign an Informed Consent Form (ICF);
  • Have histologically or cytologically documented locally advanced unresectable or metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary bladder, and urethra);
  • For Cohort A: Subjects who have radiographically confirmed disease progression during or following treatment with an anti-PD-1/PD-L1 based therapy;
  • For Cohort B: No prior chemotherapy for inoperable locally advanced or metastatic or recurrent UCa and ineligible ("unfit") for cisplatin-based chemotherapy;
  • Have measurable disease, as defined by RECIST version 1.1;
  • Have a performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) Performance Scale;
  • Have life expectancy of >/= 3 months;
  • Be willing to provide a tissue sample for pre-treatment intra-tumoral assessment of proinflammatory and immunosuppressive factors;
  • Have electrocardiogram (ECG) with no clinically significant findings as assessed by the investigator performed within 28 days prior to first dose;
  • Demonstrate adequate hematological, renal, hepatic, and coagulation function;
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of study treatment;
  • For male subjects: agreement not to father a child. Participants must be surgically sterile (e.g, vasectomy) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of study treatment.

Exclusion Criteria:

  • Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0 as well as current participation or recipient of treatment on a clinical trial within 28 days prior to Day 0;
  • Documented active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis;
  • Malignancies other than UCa within 3 years prior to Day 0, with the exception of those with negligible risk of metastasis or death treated with expected curative outcome;
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies;
  • Treatment with systemic immunostimulatory agents;
  • Treatment with systemic immunosuppressive medication;
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins;
  • Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation;
  • Active or history of autoimmune disease or immune deficiency;
  • History or any evidence of interstitial lung disease;
  • History of human immunodeficiency virus (HIV);
  • Active hepatitis B or active hepatitis C;
  • Severe infections within 4 weeks prior to enrollment;
  • Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 0;
  • History or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the trial; interfere with the subject's participation for the full duration of the trial, or is negatively impacted by EP treatment, or is not in the best interest of the subject to participate in the opinion of the treating investigator;
  • Prior allogeneic stem cell or solid organ transplant;
  • Uncontrolled tumor-related pain; pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures; or, hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.

Contact:

  • Inovio Call Center
  • 267-440-4237

Locations:

  • Alaska Clinical Research Center, LLC
  • Anchorage Alaska 99503 United States
  • Mayo Clinic Cancer Center
  • Phoenix Arizona 85054 United States
  • H. Lee Moffitt Cancer Center & Research Institute, Inc.
  • Tampa Florida 33612 United States
  • Indiana University Simon Cancer Center
  • Indianapolis Indiana 46202 United States
  • Johns Hopkins University School of Medicine
  • Baltimore Maryland 21287 United States
  • Karmanos Cancer Institute
  • Detroit Michigan 48201 United States
  • Washington University School of Medicine in St. Louis
  • Saint Louis Missouri 63110 United States
  • New York University Langone Medical Center - Perlmutter Cancer Center
  • New York New York 10016 United States
  • Weill Cornell Medical College
  • New York New York 10021 United States
  • Columbia University, Herbert Irving Comprehensive Cancer Center
  • New York New York 10032 United States
  • University of North Carolina School of Medicine
  • Chapel Hill North Carolina 27599 United States
  • University of Pittsburgh Medical Center
  • Pittsburgh Pennsylvania 15232 United States
  • Greenville Memorial Hospital
  • Greenville South Carolina 29615 United States
  • Inova Melanoma and Skin Cancer Center
  • Fairfax Virginia 22031 United States
  • Hospital de la Santa Creu i Sant Pau
  • Barcelona 08025 Spain
  • Hospital Clínic de Barcelona
  • Barcelona 08036 Spain
  • Catalan Institute of Oncology (ICO)
  • Barcelona 08908 Spain
  • Hospital Universitario 12 de Octubre
  • Madrid 28041 Spain

View trial on ClinicalTrials.gov


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A Phase II Study of Dose-Dense Gemcitabine Plus Cisplatin (ddGC) in Patients With Muscle-Invasive Bladder Cancer With Bladder Preservation for Those Patients Whose Tumors Harbor Deleterious DNA Damage Response (DDR) Gene Alterations


Condition: Infiltrating Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma, Stage III Bladder Urothelial Carcinoma

Intervention:

  • Drug: Gemcitabine Hydrochloride
  • Drug: Cisplatin
  • Biological: Pegfilgrastim
  • Procedure: Conventional Surgery
  • Procedure: Radical Cystectomy
  • Other: Chemoradiotherapy

Purpose: This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03609216

Sponsor: Alliance for Clinical Trials in Oncology

Primary Outcome Measures:

  • Measure: Proportion of patients who are recurrence-free within the DDR mutated group who undergo the bladder sparing approach
  • Time Frame: At 3 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Clinical response rate for patients harboring deleterious DDR gene alterations
  • Time Frame: After 6 courses (84 days)
  • Safety Issue:
  • Measure: Bladder-intact survival in DDR-altered patients with < cT1 responses who selected the bladder sparing approach
  • Time Frame: Time from registration up to 5 years
  • Safety Issue:
  • Measure: Overall survival
  • Time Frame: Time from study registration up to 5 years
  • Safety Issue:
  • Measure: Pathologic response (pT0) rate at cystectomy in participants without DDR gene alterations
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Recurrence-free survival
  • Time Frame: Time from study registration up to 5 years
  • Safety Issue:
  • Measure: The rate of cystectomies in patients with a DDR alteration and with a cT0/CIS/Ta response
  • Time Frame: Within 3 years
  • Safety Issue:
  • Measure: Proportion of patients in the bladder-sparing group who undergo local therapy
  • Time Frame: Up to 5 years
  • Safety Issue:

Estimated Enrollment: 271

Study Start Date: August 1, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Step 1 Patient Registration Eligibility Criteria
  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
  • 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
  • Clinical stage T2-T4aN0/xM0 disease
  • Medically appropriate candidate for radical cystectomy as assessed by surgeon
  • No concomitant multifocal carcinoma in situ; a single focus is allowed
  • One focus of muscle-invasive bladder cancer and/or a tumor < 5 cm in size
  • No clinical or radiographic evidence for locally advanced or metastatic disease
  • No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x 6 treatments; BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed)
  • No prior radiation therapy to the bladder
  • No major surgery or radiation therapy =< 4 weeks of registration
  • Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Calculated creatinine clearance >= 55 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) * (For patients with documented Gilbert's syndrome bilirubin =< 3 x ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • No hydronephrosis refractory to urinary diversion
  • No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
  • No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
  • No pre-existing sensory grade >= 2 neuropathy
  • No pre-existing grade >= 2 hearing loss
  • No serious intercurrent medical or psychiatric illness, including serious active infection
  • None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
  • No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
  • No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
  • No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
  • Step 2 Patient Registration Eligibility Criteria
  • Patients must have completed 4 or more cycles of protocol-directed chemotherapy
  • Step 3 Patient Registration

Eligibility Criteria:

  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
  • 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
  • Clinical stage T2-T4aN0/xM0 disease
  • Medically appropriate candidate for radical cystectomy as assessed by surgeon
  • No concomitant multifocal carcinoma in situ; a single focus is allowed
  • One focus of muscle-invasive bladder cancer and/or a tumor < 5 cm in size
  • No clinical or radiographic evidence for locally advanced or metastatic disease
  • No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x 6 treatments; BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed)
  • No prior radiation therapy to the bladder
  • No major surgery or radiation therapy =< 4 weeks of registration
  • Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Calculated creatinine clearance >= 55 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) * (For patients with documented Gilbert's syndrome bilirubin =< 3 x ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • No hydronephrosis refractory to urinary diversion
  • No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
  • No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
  • No pre-existing sensory grade >= 2 neuropathy
  • No pre-existing grade >= 2 hearing loss
  • No serious intercurrent medical or psychiatric illness, including serious active infection
  • None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
  • No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
  • No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
  • No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
  • Step 2 Patient Registration Eligibility Criteria
  • Patients must have completed 4 or more cycles of protocol-directed chemotherapy
  • Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene alteration)
  • Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pre-treatment TURBT deoxyribonucleic acid (DNA)
  • Cystoscopy and imaging performed to determine stage/treatment assignment

Contact:

  • Gopa Iyer, MD
  • 646-888-4737

Locations:

  • CHI Saint Vincent Cancer Center Hot Springs
  • Hot Springs Arkansas 71913 United States
  • Fremont - Rideout Cancer Center
  • Marysville California 95901 United States
  • University of California Davis Comprehensive Cancer Center
  • Sacramento California 95817 United States
  • Penrose-Saint Francis Healthcare
  • Colorado Springs Colorado 80907 United States
  • Rocky Mountain Cancer Centers-Penrose
  • Colorado Springs Colorado 80907 United States
  • Porter Adventist Hospital
  • Denver Colorado 80210 United States
  • Mercy Medical Center
  • Durango Colorado 81301 United States
  • Southwest Oncology PC
  • Durango Colorado 81301 United States
  • Mountain Blue Cancer Care Center
  • Golden Colorado 80401 United States
  • Rocky Mountain Cancer Centers-Lakewood
  • Lakewood Colorado 80228 United States
  • Saint Anthony Hospital
  • Lakewood Colorado 80228 United States
  • Littleton Adventist Hospital
  • Littleton Colorado 80122 United States
  • Longmont United Hospital
  • Longmont Colorado 80501 United States
  • Rocky Mountain Cancer Centers-Longmont
  • Longmont Colorado 80501 United States
  • Parker Adventist Hospital
  • Parker Colorado 80138 United States
  • Rocky Mountain Cancer Centers-Parker
  • Parker Colorado 80138 United States
  • Saint Mary Corwin Medical Center
  • Pueblo Colorado 81004 United States
  • Rocky Mountain Cancer Centers - Pueblo
  • Pueblo Colorado 81008 United States
  • Rocky Mountain Cancer Centers-Thornton
  • Thornton Colorado 80260 United States
  • University of Florida Health Science Center - Gainesville
  • Gainesville Florida 32610 United States
  • Saint Alphonsus Cancer Care Center-Boise
  • Boise Idaho 83706 United States
  • Saint Alphonsus Cancer Care Center-Caldwell
  • Caldwell Idaho 83605 United States
  • Kootenai Medical Center
  • Coeur d'Alene Idaho 83814 United States
  • Walter Knox Memorial Hospital
  • Emmett Idaho 83617 United States
  • Idaho Urologic Institute-Meridian
  • Meridian Idaho 83642 United States
  • Saint Alphonsus Medical Center-Nampa
  • Nampa Idaho 83686 United States
  • Kootenai Cancer Center
  • Post Falls Idaho 83854 United States
  • Kootenai Cancer Clinic
  • Sandpoint Idaho 83864 United States
  • Illinois CancerCare-Bloomington
  • Bloomington Illinois 61704 United States
  • Illinois CancerCare-Canton
  • Canton Illinois 61520 United States
  • Memorial Hospital of Carbondale
  • Carbondale Illinois 62902 United States
  • SIH Cancer Institute
  • Carterville Illinois 62918 United States
  • Illinois CancerCare-Carthage
  • Carthage Illinois 62321 United States
  • Centralia Oncology Clinic
  • Centralia Illinois 62801 United States
  • Cancer Care Specialists of Illinois - Decatur
  • Decatur Illinois 62526 United States
  • Decatur Memorial Hospital
  • Decatur Illinois 62526 United States
  • Crossroads Cancer Center
  • Effingham Illinois 62401 United States
  • Illinois CancerCare-Eureka
  • Eureka Illinois 61530 United States
  • Illinois CancerCare-Galesburg
  • Galesburg Illinois 61401 United States
  • Western Illinois Cancer Treatment Center
  • Galesburg Illinois 61401 United States
  • Illinois CancerCare-Kewanee Clinic
  • Kewanee Illinois 61443 United States
  • Illinois CancerCare-Macomb
  • Macomb Illinois 61455 United States
  • Illinois CancerCare-Ottawa Clinic
  • Ottawa Illinois 61350 United States
  • Illinois CancerCare-Pekin
  • Pekin Illinois 61554 United States
  • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
  • Pekin Illinois 61554 United States
  • Illinois CancerCare-Peoria
  • Peoria Illinois 61615 United States
  • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
  • Peoria Illinois 61615 United States
  • Methodist Medical Center of Illinois
  • Peoria Illinois 61636 United States
  • OSF Saint Francis Medical Center
  • Peoria Illinois 61637 United States
  • Illinois CancerCare-Peru
  • Peru Illinois 61354 United States
  • Valley Radiation Oncology
  • Peru Illinois 61354 United States
  • Illinois CancerCare-Princeton
  • Princeton Illinois 61356 United States
  • Southern Illinois University School of Medicine
  • Springfield Illinois 62702 United States
  • Springfield Clinic
  • Springfield Illinois 62702 United States
  • Memorial Medical Center
  • Springfield Illinois 62781 United States
  • Cancer Care Specialists of Illinois-Swansea
  • Swansea Illinois 62226 United States
  • Southwest Illinois Health Services LLP
  • Swansea Illinois 62226 United States
  • Reid Health
  • Richmond Indiana 47374 United States
  • Medical Oncology and Hematology Associates-West Des Moines
  • Clive Iowa 50325 United States
  • Mercy Cancer Center-West Lakes
  • Clive Iowa 50325 United States
  • Alegent Health Mercy Hospital
  • Council Bluffs Iowa 51503 United States
  • Greater Regional Medical Center
  • Creston Iowa 50801 United States
  • Iowa Methodist Medical Center
  • Des Moines Iowa 50309 United States
  • Medical Oncology and Hematology Associates-Des Moines
  • Des Moines Iowa 50309 United States
  • Broadlawns Medical Center
  • Des Moines Iowa 50314 United States
  • Medical Oncology and Hematology Associates-Laurel
  • Des Moines Iowa 50314 United States
  • Mercy Medical Center - Des Moines
  • Des Moines Iowa 50314 United States
  • Iowa Lutheran Hospital
  • Des Moines Iowa 50316 United States
  • Trinity Regional Medical Center
  • Fort Dodge Iowa 50501 United States
  • Methodist West Hospital
  • West Des Moines Iowa 50266-7700 United States
  • Mercy Medical Center-West Lakes
  • West Des Moines Iowa 50266 United States
  • Flaget Memorial Hospital
  • Bardstown Kentucky 40004 United States
  • Commonwealth Cancer Center-Corbin
  • Corbin Kentucky 40701 United States
  • Saint Joseph Radiation Oncology Resource Center
  • Lexington Kentucky 40504 United States
  • Saint Joseph Hospital East
  • Lexington Kentucky 40509 United States
  • Saint Joseph London
  • London Kentucky 40741 United States
  • Jewish Hospital
  • Louisville Kentucky 40202 United States
  • Saints Mary and Elizabeth Hospital
  • Louisville Kentucky 40215 United States
  • Jewish Hospital Medical Center Northeast
  • Louisville Kentucky 40245 United States
  • Jewish Hospital Medical Center South
  • Shepherdsville Kentucky 40165 United States
  • East Jefferson General Hospital
  • Metairie Louisiana 70006 United States
  • Louisiana State University Health Science Center
  • New Orleans Louisiana 70112 United States
  • University Medical Center New Orleans
  • New Orleans Louisiana 70112 United States
  • Ochsner Medical Center Jefferson
  • New Orleans Louisiana 70121 United States
  • Mercy Medical Center
  • Springfield Massachusetts 01104 United States
  • Saint Joseph Mercy Hospital
  • Ann Arbor Michigan 48106 United States
  • IHA Hematology Oncology Consultants-Brighton
  • Brighton Michigan 48114 United States
  • Saint Joseph Mercy Brighton
  • Brighton Michigan 48114 United States
  • IHA Hematology Oncology Consultants-Canton
  • Canton Michigan 48188 United States
  • Saint Joseph Mercy Canton
  • Canton Michigan 48188 United States
  • Caro Cancer Center
  • Caro Michigan 48723 United States
  • IHA Hematology Oncology Consultants-Chelsea
  • Chelsea Michigan 48118 United States
  • Saint Joseph Mercy Chelsea
  • Chelsea Michigan 48118 United States
  • Hematology Oncology Consultants-Clarkston
  • Clarkston Michigan 48346 United States
  • Newland Medical Associates-Clarkston
  • Clarkston Michigan 48346 United States
  • Ascension Saint John Hospital
  • Detroit Michigan 48236 United States
  • Great Lakes Cancer Management Specialists-Doctors Park
  • East China Township Michigan 48054 United States
  • Genesee Cancer and Blood Disease Treatment Center
  • Flint Michigan 48503 United States
  • Genesee Hematology Oncology PC
  • Flint Michigan 48503 United States
  • Genesys Hurley Cancer Institute
  • Flint Michigan 48503 United States
  • Hurley Medical Center
  • Flint Michigan 48503 United States
  • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
  • Grosse Pointe Woods Michigan 48236 United States
  • Lymphoma Clinic of Michigan
  • Grosse Pointe Woods Michigan 48236 United States
  • Michigan Breast Specialists-Grosse Pointe Woods
  • Grosse Pointe Woods Michigan 48236 United States
  • Sparrow Hospital
  • Lansing Michigan 48912 United States
  • Hope Cancer Clinic
  • Livonia Michigan 48154 United States
  • Saint Mary Mercy Hospital
  • Livonia Michigan 48154 United States
  • Great Lakes Cancer Management Specialists-Macomb Medical Campus
  • Macomb Michigan 48044 United States
  • Michigan Breast Specialists-Macomb Township
  • Macomb Michigan 48044 United States
  • Saint Mary's Oncology/Hematology Associates of Marlette
  • Marlette Michigan 48453 United States
  • 21st Century Oncology-Pontiac
  • Pontiac Michigan 48341 United States
  • Hope Cancer Center
  • Pontiac Michigan 48341 United States
  • Newland Medical Associates-Pontiac
  • Pontiac Michigan 48341 United States
  • Saint Joseph Mercy Oakland
  • Pontiac Michigan 48341 United States
  • Great Lakes Cancer Management Specialists-Rochester Hills
  • Rochester Hills Michigan 48309 United States
  • Saint Mary's of Michigan
  • Saginaw Michigan 48601 United States
  • Oncology Hematology Associates of Saginaw Valley PC
  • Saginaw Michigan 48604 United States
  • Bhadresh Nayak MD PC-Sterling Heights
  • Sterling Heights Michigan 48312 United States
  • Saint Joseph Health System-Tawas City
  • Tawas City Michigan 48764 United States
  • Advanced Breast Care Center PLLC
  • Warren Michigan 48088 United States
  • Great Lakes Cancer Management Specialists-Macomb Professional Building
  • Warren Michigan 48093 United States
  • Macomb Hematology Oncology PC
  • Warren Michigan 48093 United States
  • Michigan Breast Specialists-Warren
  • Warren Michigan 48093 United States
  • Saint John Macomb-Oakland Hospital
  • Warren Michigan 48093 United States
  • Saint Mary's Oncology/Hematology Associates of West Branch
  • West Branch Michigan 48661 United States
  • Huron Gastroenterology PC
  • Ypsilanti Michigan 48106 United States
  • IHA Hematology Oncology Consultants-Ann Arbor
  • Ypsilanti Michigan 48197 United States
  • Sanford Joe Lueken Cancer Center
  • Bemidji Minnesota 56601 United States
  • Essentia Health Saint Joseph's Medical Center
  • Brainerd Minnesota 56401 United States
  • Fairview Ridges Hospital
  • Burnsville Minnesota 55337 United States
  • Mercy Hospital
  • Coon Rapids Minnesota 55433 United States
  • Essentia Health - Deer River Clinic
  • Deer River Minnesota 56636 United States
  • Essentia Health Saint Mary's - Detroit Lakes Clinic
  • Detroit Lakes Minnesota 56501 United States
  • Essentia Health Cancer Center
  • Duluth Minnesota 55805 United States
  • Essentia Health Saint Mary's Medical Center
  • Duluth Minnesota 55805 United States
  • Miller-Dwan Hospital
  • Duluth Minnesota 55805 United States
  • Fairview-Southdale Hospital
  • Edina Minnesota 55435 United States
  • Lake Region Healthcare Corporation-Cancer Care
  • Fergus Falls Minnesota 56537 United States
  • Essentia Health - Fosston
  • Fosston Minnesota 56542 United States
  • Unity Hospital
  • Fridley Minnesota 55432 United States
  • Essentia Health Hibbing Clinic
  • Hibbing Minnesota 55746 United States
  • Fairview Maple Grove Medical Center
  • Maple Grove Minnesota 55369 United States
  • Minnesota Oncology Hematology PA-Maplewood
  • Maplewood Minnesota 55109 United States
  • Saint John's Hospital - Healtheast
  • Maplewood Minnesota 55109 United States
  • Abbott-Northwestern Hospital
  • Minneapolis Minnesota 55407 United States
  • Hennepin County Medical Center
  • Minneapolis Minnesota 55415 United States
  • Health Partners Inc
  • Minneapolis Minnesota 55454 United States
  • Monticello Cancer Center
  • Monticello Minnesota 55362 United States
  • New Ulm Medical Center
  • New Ulm Minnesota 56073 United States
  • Essentia Health - Park Rapids
  • Park Rapids Minnesota 56470 United States
  • North Memorial Medical Health Center
  • Robbinsdale Minnesota 55422 United States
  • Park Nicollet Clinic - Saint Louis Park
  • Saint Louis Park Minnesota 55416 United States
  • Regions Hospital
  • Saint Paul Minnesota 55101 United States
  • United Hospital
  • Saint Paul Minnesota 55102 United States
  • Essentia Health Sandstone
  • Sandstone Minnesota 55072 United States
  • Saint Francis Regional Medical Center
  • Shakopee Minnesota 55379 United States
  • Lakeview Hospital
  • Stillwater Minnesota 55082 United States
  • Sanford Thief River Falls Medical Center
  • Thief River Falls Minnesota 56701 United States
  • Essentia Health Virginia Clinic
  • Virginia Minnesota 55792 United States
  • Ridgeview Medical Center
  • Waconia Minnesota 55387 United States
  • Rice Memorial Hospital
  • Willmar Minnesota 56201 United States
  • Minnesota Oncology Hematology PA-Woodbury
  • Woodbury Minnesota 55125 United States
  • Sanford Cancer Center Worthington
  • Worthington Minnesota 56187 United States
  • Fairview Lakes Medical Center
  • Wyoming Minnesota 55092 United States
  • Parkland Health Center-Bonne Terre
  • Bonne Terre Missouri 63628 United States
  • Saint Francis Medical Center
  • Cape Girardeau Missouri 63703 United States
  • Southeast Cancer Center
  • Cape Girardeau Missouri 63703 United States
  • Siteman Cancer Center at West County Hospital
  • Creve Coeur Missouri 63141 United States
  • Capital Region Southwest Campus
  • Jefferson City Missouri 65109 United States
  • Washington University School of Medicine
  • Saint Louis Missouri 63110 United States
  • Siteman Cancer Center-South County
  • Saint Louis Missouri 63129 United States
  • Missouri Baptist Medical Center
  • Saint Louis Missouri 63131 United States
  • Sainte Genevieve County Memorial Hospital
  • Sainte Genevieve Missouri 63670 United States
  • Missouri Baptist Sullivan Hospital
  • Sullivan Missouri 63080 United States
  • Missouri Baptist Outpatient Center-Sunset Hills
  • Sunset Hills Missouri 63127 United States
  • Community Hospital of Anaconda
  • Anaconda Montana 59711 United States
  • Billings Clinic Cancer Center
  • Billings Montana 59101 United States
  • Bozeman Deaconess Hospital
  • Bozeman Montana 59715 United States
  • Benefis Healthcare- Sletten Cancer Institute
  • Great Falls Montana 59405 United States
  • Great Falls Clinic
  • Great Falls Montana 59405 United States
  • Saint Peter's Community Hospital
  • Helena Montana 59601 United States
  • Kalispell Regional Medical Center
  • Kalispell Montana 59901 United States
  • Community Medical Hospital
  • Missoula Montana 59804 United States
  • CHI Health Saint Francis
  • Grand Island Nebraska 68803 United States
  • Heartland Hematology and Oncology
  • Kearney Nebraska 68845 United States
  • CHI Health Good Samaritan
  • Kearney Nebraska 68847 United States
  • Saint Elizabeth Regional Medical Center
  • Lincoln Nebraska 68510 United States
  • Alegent Health Immanuel Medical Center
  • Omaha Nebraska 68122 United States
  • Hematology and Oncology Consultants PC
  • Omaha Nebraska 68122 United States
  • Alegent Health Bergan Mercy Medical Center
  • Omaha Nebraska 68124 United States
  • Alegent Health Lakeside Hospital
  • Omaha Nebraska 68130 United States
  • Creighton University Medical Center
  • Omaha Nebraska 68131 United States
  • Midlands Community Hospital
  • Papillion Nebraska 68046 United States
  • Memorial Sloan Kettering Basking Ridge
  • Basking Ridge New Jersey 07920 United States
  • Englewood Hospital and Medical Center
  • Englewood New Jersey 07631 United States
  • Memorial Sloan Kettering Monmouth
  • Middletown New Jersey 07748 United States
  • Memorial Sloan Kettering Bergen
  • Montvale New Jersey 07645 United States
  • Roswell Park Cancer Institute
  • Buffalo New York 14263 United States
  • Memorial Sloan Kettering Commack
  • Commack New York 11725 United States
  • Memorial Sloan Kettering Westchester
  • Harrison New York 10604 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States
  • Memorial Sloan Kettering Rockville Centre
  • Rockville Centre New York 11570 United States
  • State University of New York Upstate Medical University
  • Syracuse New York 13210 United States
  • Southeastern Medical Oncology Center-Clinton
  • Clinton North Carolina 28328 United States
  • Southeastern Medical Oncology Center-Goldsboro
  • Goldsboro North Carolina 27534 United States
  • Wayne Memorial Hospital
  • Goldsboro North Carolina 27534 United States
  • Onslow Memorial Hospital
  • Jacksonville North Carolina 28546 United States
  • Southeastern Medical Oncology Center-Jacksonville
  • Jacksonville North Carolina 28546 United States
  • Sanford Bismarck Medical Center
  • Bismarck North Dakota 58501 United States
  • Essentia Health Cancer Center-South University Clinic
  • Fargo North Dakota 58103 United States
  • Sanford South University Medical Center
  • Fargo North Dakota 58103 United States
  • Sanford Medical Center Fargo
  • Fargo North Dakota 58104 United States
  • Roger Maris Cancer Center
  • Fargo North Dakota 58122 United States
  • Sanford Broadway Medical Center
  • Fargo North Dakota 58122 United States
  • Essentia Health - Jamestown Clinic
  • Jamestown North Dakota 58401 United States
  • Indu and Raj Soin Medical Center
  • Beavercreek Ohio 45431 United States
  • Dayton Physicians LLC-Miami Valley South
  • Centerville Ohio 45459 United States
  • Miami Valley Hospital South
  • Centerville Ohio 45459 United States
  • Good Samaritan Hospital - Cincinnati
  • Cincinnati Ohio 45220 United States
  • Oncology Hematology Care Inc-Kenwood
  • Cincinnati Ohio 45236 United States
  • Bethesda North Hospital
  • Cincinnati Ohio 45242 United States
  • TriHealth Cancer Institute-Westside
  • Cincinnati Ohio 45247 United States
  • TriHealth Cancer Institute-Anderson
  • Cincinnati Ohio 45255 United States
  • Good Samaritan Hospital - Dayton
  • Dayton Ohio 45406 United States
  • Miami Valley Hospital
  • Dayton Ohio 45409 United States
  • Dayton Physician LLC-Miami Valley Hospital North
  • Dayton Ohio 45415 United States
  • Miami Valley Hospital North
  • Dayton Ohio 45415 United States
  • Armes Family Cancer Center
  • Findlay Ohio 45840 United States
  • Blanchard Valley Hospital
  • Findlay Ohio 45840 United States
  • Orion Cancer Care
  • Findlay Ohio 45840 United States
  • Atrium Medical Center-Middletown Regional Hospital
  • Franklin Ohio 45005-1066 United States
  • Dayton Physicians LLC-Atrium
  • Franklin Ohio 45005 United States
  • Dayton Physicians LLC-Wayne
  • Greenville Ohio 45331 United States
  • Wayne Hospital
  • Greenville Ohio 45331 United States
  • Greater Dayton Cancer Center
  • Kettering Ohio 45409 United States
  • First Dayton Cancer Care
  • Kettering Ohio 45420 United States
  • Kettering Medical Center
  • Kettering Ohio 45429 United States
  • Springfield Regional Cancer Center
  • Springfield Ohio 45504 United States
  • Springfield Regional Medical Center
  • Springfield Ohio 45505 United States
  • Dayton Physicians LLC-Upper Valley
  • Troy Ohio 45373 United States
  • Upper Valley Medical Center
  • Troy Ohio 45373 United States
  • University of Oklahoma Health Sciences Center
  • Oklahoma City Oklahoma 73104 United States
  • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Tulsa Oklahoma 74146 United States
  • Saint Alphonsus Medical Center-Baker City
  • Baker City Oregon 97814 United States
  • Saint Alphonsus Medical Center-Ontario
  • Ontario Oregon 97914 United States
  • Lehigh Valley Hospital-Cedar Crest
  • Allentown Pennsylvania 18103 United States
  • Lehigh Valley Hospital - Muhlenberg
  • Bethlehem Pennsylvania 18017 United States
  • Pocono Medical Center
  • East Stroudsburg Pennsylvania 18301 United States
  • Lehigh Valley Hospital-Hazleton
  • Hazleton Pennsylvania 18201 United States
  • Greenville Health System Cancer Institute-Laurens
  • Clinton South Carolina 29325 United States
  • Greenville Health System Cancer Institute-Easley
  • Easley South Carolina 29640 United States
  • Greenville Health System Cancer Institute-Butternut
  • Greenville South Carolina 29605 United States
  • Greenville Health System Cancer Institute-Faris
  • Greenville South Carolina 29605 United States
  • Greenville Memorial Hospital
  • Greenville South Carolina 29605 United States
  • Greenville Health System Cancer Institute-Eastside
  • Greenville South Carolina 29615 United States
  • Greenville Health System Cancer Institute-Greer
  • Greer South Carolina 29650 United States
  • Greenville Health System Cancer Institute-Seneca
  • Seneca South Carolina 29672 United States
  • Greenville Health System Cancer Institute-Spartanburg
  • Spartanburg South Carolina 29307 United States
  • Sanford Cancer Center Oncology Clinic
  • Sioux Falls South Dakota 57104 United States
  • Sanford USD Medical Center - Sioux Falls
  • Sioux Falls South Dakota 57117-5134 United States
  • Memorial Hospital
  • Chattanooga Tennessee 37404 United States
  • Pulmonary Medicine Center of Chattanooga-Hixson
  • Hixson Tennessee 37343 United States
  • Memorial GYN Plus
  • Ooltewah Tennessee 37363 United States
  • Saint Joseph Regional Cancer Center
  • Bryan Texas 77802 United States
  • Harrison HealthPartners Hematology and Oncology-Bremerton
  • Bremerton Washington 98310 United States
  • Harrison Medical Center
  • Bremerton Washington 98310 United States
  • Highline Medical Center-Main Campus
  • Burien Washington 98166 United States
  • Saint Elizabeth Hospital
  • Enumclaw Washington 98022 United States
  • Saint Francis Hospital
  • Federal Way Washington 98003 United States
  • Saint Clare Hospital
  • Lakewood Washington 98499 United States
  • Harrison HealthPartners Hematology and Oncology-Poulsbo
  • Poulsbo Washington 98370 United States
  • Franciscan Research Center-Northwest Medical Plaza
  • Tacoma Washington 98405 United States
  • Northwest Medical Specialties PLLC
  • Tacoma Washington 98405 United States
  • United Hospital Center
  • Bridgeport West Virginia 26330 United States
  • WVUH-Berkely Medical Center
  • Martinsburg West Virginia 25401 United States
  • West Virginia University Healthcare
  • Morgantown West Virginia 26506 United States
  • Camden Clark Medical Center
  • Parkersburg West Virginia 26101 United States
  • Duluth Clinic Ashland
  • Ashland Wisconsin 54806 United States
  • Northwest Wisconsin Cancer Center
  • Ashland Wisconsin 54806 United States
  • Marshfield Clinic Cancer Center - Eau Claire
  • Eau Claire Wisconsin 54701 United States
  • Cancer Center of Western Wisconsin
  • New Richmond Wisconsin 54017 United States
  • Billings Clinic-Cody
  • Cody Wyoming 82414 United States
  • Welch Cancer Center
  • Sheridan Wyoming 82801 United States

View trial on ClinicalTrials.gov


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A Multicenter Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of the Combination of Rogaratinib and Copanlisib in Patients With FGFR-positive, Locally Advanced or Metastatic Solid Tumors


Condition: Advanced or Metastatic Solid Tumor

Intervention:

  • Drug: Rogaratinib (BAY1163877)
  • Drug: Copanlisib (BAY80-6946)

Purpose: The primary objective of this study is to determine the safety, tolerability, maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) and efficacy of rogaratinib in combination with copanlisib in patients with locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype. The secondary objectives of this study are to characterize the pharmacokinetics (PK) of rogaratinib and copanlisib alone and in combination, and to assess the anti-tumor efficacy of rogaratinib in combination with copanlisib locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03517956

Sponsor: Bayer

Primary Outcome Measures:

  • Measure: Incidence of treatment-emergent adverse events (TEAEs)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of drug-related TEAEs
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of treatment-emergent serious adverse events (TESAEs)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of Dose-limiting toxicities (DLTs)
  • Time Frame: Approximately 10 months
  • Safety Issue:
  • Measure: Objective response rate (ORR) at recommended dose
  • Time Frame: Up to 22 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Maximum plasma concentration of Copanlisib (Cmax)
  • Time Frame: 0 (pre-dose), 0.5, 1 (end of infusion), 2, 4, 8, 24, 48 hours after drug administration (Days 1, 2, 3) and 0, 0.5, 1, 2, 4, 8, 24, 48 hours after drug administration (Days 15, 16, 17) in dose escalation
  • Safety Issue:
  • Measure: Area under the plasma concentration versus time curve of Copanlisib (AUC (0-48))
  • Time Frame: 0 (pre-dose), 0.5, 1 (end of infusion), 2, 4, 8, 24, 48 hours after drug administration (Days 1, 2, 3) and 0, 0.5, 1, 2, 4, 8, 24, 48 hours after drug administration (Days 15, 16, 17) in dose escalation
  • Safety Issue:
  • Measure: Area under the plasma concentration versus time curve of Rogaratinib (AUC (0-8))
  • Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8 hours after drug (Day 14) and 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24, 48 hours after drug (Days 15 to 17) in dose escalation; 0 (pre-dose) and 1 hour after drug on Day 1 of dose expansion
  • Safety Issue:
  • Measure: Maximum plasma concentration of Rogaratinib (Cmax)
  • Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8 hours after drug (Day 14) and 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24, 48 hours after drug (Days 15 to 17) in dose escalation; 0 (pre-dose) and 1 hour after drug on Day 1 of dose expansion
  • Safety Issue:
  • Measure: Objective response rate (ORR)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Disease control rate (DCR)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Duration of response (DOR) for Partial Response and Complete Response
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Progression-free survival (PFS)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Overall survival (OS)
  • Time Frame: Up to 32 months
  • Safety Issue:

Estimated Enrollment: 65

Study Start Date: July 25, 2018

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • High FGFR mRNA expression levels (RNAscope score of ≥3; measurement is part of this protocol) in archival or fresh tumor biopsy specimen.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in contrast enhanced (unless contraindicated) CT or MRI.
  • Adequate bone marrow, liver and renal function.
  • Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) formula.
  • Left ventricular ejection fraction (LVEF) equal to or above the lower limit of normal (LLN) at the institution.
  • Life expectancy of at least 3 months.
  • For the dose escalation part: Patients with histologically confirmed, locally advanced or metastatic solid tumors who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anti-cancer treatment is no longer effective, excluding primary brain or spinal tumors. Patients who have been advised with all standard treatment options and still refuse them must be documented and can be allowed to enter the trial.
  • For the dose expansion part: Patients with histologically confirmed, locally advanced or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anticancer treatment is no longer effective. Patients who have been advised with all standard treatment options and still refuse them must be documented and can be allowed to enter the trial.

Exclusion Criteria:

  • Previous or concurrent cancer that is distinct from tumor for which the patient is enrolled in study, with exceptions
  • Ongoing or previous anti-cancer treatment within 4 weeks of study treatment start (or 6 weeks for mitomycin C, nitrosoureas and monoclonal antibodies); with exceptions.
  • Prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to treatment discontinuation (previous exposure is allowed in other circumstances). If prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to treatment discontinuation is different from the known safety profile of rogaratinib or copanlisib, enrollment is allowed.
  • Symptomatic brain or meningeal metastatic tumors unless the patient is >6 months from definitive therapy, has no evidence of tumor growth on an imaging study and is clinically stable with respect to the tumor at the start of study treatment. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies).
  • History or current condition of an uncontrolled cardiovascular disease including congestive heart failure NYHA > Class 2, unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months) or myocardial infarction within past 6 months and cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).
  • Active hepatitis B (HBV) or C (HCV) infection.
  • Active clinically serious infections (≥ CTCAE v4.03 Grade 2).

Contact:

  • Bayer Clinical Trials Contact
  • (+)1-888-84 22937

Locations:

  • USC Norris Hospital and Clinics
  • Los Angeles California 90033 United States
  • Northwestern University
  • Chicago Illinois 60611 United States
  • University of Maryland
  • Baltimore Maryland 12101 United States
  • Dana-Farber Cancer Institute
  • Boston Massachusetts 02215 United States
  • Barbara Ann Karmanos Cancer Institute
  • Detroit Michigan 48201 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89169 United States
  • Memorial Sloan-Kettering Cancer Center
  • New York New York 10065 United States
  • Greenville Health System
  • Greenville South Carolina 29605 United States
  • Texas Oncology- Austin Midtown
  • Austin Texas 78705 United States
  • Tyler Cancer Center
  • Tyler Texas 75702 United States
  • CU Saint-Luc/UZ St-Luc
  • Bruxelles - Brussel 1200 Belgium
  • UZ Antwerpen
  • Edegem 2650 Belgium
  • CHU de Liège
  • Liege 4000 Belgium
  • Centre Oscar Lambret - Lille
  • LILLE cedex 59020 France
  • Centre Léon Bérard
  • Lyon Cedex 69008 France
  • Krankenhaus Nordwest
  • Frankfurt Hessen 60488 Germany
  • Universitätsklinikum Köln
  • Köln Nordrhein-Westfalen 50937 Germany
  • Universitätsklinikum Hamburg Eppendorf (UKE)
  • Hamburg 20246 Germany
  • Klinikum der Universität Würzburg
  • Würzburg 97080 Germany
  • Asan Medical Center
  • Seoul 05505 Korea, Republic of
  • Samsung Medical Center
  • Seoul 06351 Korea, Republic of
  • Yonsei University College of Medicine
  • Seoul 120-752 Korea, Republic of
  • National University Hospital
  • Singapore 119074 Singapore
  • National Cancer Center
  • Singapore 169610 Singapore
  • Ciutat Sanitària i Universitaria de la Vall d'Hebron
  • Barcelona 08035 Spain
  • Hospital Clínic i Provincial de Barcelona
  • Barcelona 08036 Spain
  • Hospital General Universitario Gregorio Marañón
  • Madrid 28007 Spain
  • MD Anderson International Espanya, S.A.
  • Madrid 28033 Spain
  • Hospital Clínico Universitario de Valencia
  • Valencia 46010 Spain

View trial on ClinicalTrials.gov


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A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients With Advanced or Metastatic Urothelial Carcinoma


Condition: Urothelial Carcinoma, Urothelial Carcinoma Bladder, Urothelial Carcinoma Ureter, Urothelial Carcinoma of the Renal Pelvis and Ureter, Urothelial Carcinoma Urethra

Intervention:

  • Drug: Sitravatinib
  • Drug: Nivolumab

Purpose: The study will evaluate the clinical activity of nivolumab in combination with the investigational agent sitravatinib in patients with advanced or metastatic urothelial carcinoma.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03606174

Sponsor: Mirati Therapeutics Inc.

Primary Outcome Measures:

  • Measure: Number of patients experiencing tumor size reduction
  • Time Frame: up to 3 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Number of patients experiencing adverse events
  • Time Frame: up to 12 months
  • Safety Issue:
  • Measure: Blood plasma concentration of the investigational agent
  • Time Frame: up to 20 weeks
  • Safety Issue:

Estimated Enrollment: 80

Study Start Date: September 11, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Diagnosis of urothelial carcinoma
  • Most recent treatment must have included a checkpoint inhibitor
  • Adequate bone marrow and organ function

Exclusion Criteria:

  • Uncontrolled tumor in the brain
  • Unacceptable toxicity with prior checkpoint inhibitor
  • Impaired heart function

Contact:

  • Mirati Therapeutics Study Locator Services
  • 1-844-893-5530 (toll free)

Locations:

  • Rocky Mountain Cancer Centers-Aurora
  • Aurora Colorado 80012 United States
  • SCRI - Florida Cancer Specialists- North Region
  • Saint Petersburg Florida 33705 United States
  • Florida Cancer Specialist-West Palm Beach
  • West Palm Beach Florida 33401 United States
  • Washington University in St Louis
  • Saint Louis Missouri 63110 United States
  • GU Research Network/Urology Cancer Center
  • Omaha Nebraska 68130 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89169 United States
  • New York Oncology Hematology
  • Albany New York 12206 United States
  • The Ohio State University
  • Columbus Ohio 43202 United States
  • Allegheny Singer Research Institute
  • Pittsburgh Pennsylvania 15212 United States
  • Texas Oncology-Austin Central
  • Austin Texas 78731 United States
  • Texas Oncology- Memorial City
  • Houston Texas 77024 United States
  • MD Anderson Cancer Center
  • Houston Texas 77030 United States
  • Texas Oncology - Tyler
  • Tyler Texas 75702 United States
  • Virginia Cancer Specialists- Fairfax
  • Fairfax Virginia 22031 United States

View trial on ClinicalTrials.gov


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A Phase I/II Study of IMCnyeso, HLA- A*0201-Restricted, NY-ESO-1- and LAGE-1A-specific Soluble T Cell Receptor and Anti-CD3 Bispecific Molecule, in HLA-A*0201 Positive Patients With Advanced NY-ESO-1 and/or LAGE - 1A Positive Cancer


Condition: Melanoma, Advanced NSCLC, Urothelial Carcinoma, Synovial Sarcoma

Intervention:

  • Drug: IMCnyeso
  • Drug: IMCnyeso

Purpose: IMCnyeso is a new biological therapy designed for the treatment of cancers which express NY-ESO-1 and/or LAGE-1A. This is a first-in-human trial designed to evaluate the safety and efficacy of IMCnyeso in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for NY-ESO-1 and/or LAGE-A1.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03515551

Sponsor: Immunocore Ltd

Primary Outcome Measures:

  • Measure: Recommended phase 2 dose (RP2D)
  • Time Frame: From day 1 to day 28 of treatment
  • Safety Issue:
  • Measure: Number of patients with treatment emergent AEs
  • Time Frame: Safety will be assessed from informed consent through 90 days after end of treatment
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Objective response rate (ORR) defined as the proportion of patients achieving an objective response (RECIST v1.1 and modified irRECIST) (Arm 2 only)
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Disease control rate (DCR) defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1 and modified irRECIST). (Part 2 only)
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Pharmacokinetics
  • Time Frame: 2 weeks (AUC will be assessed weekly for 2 weeks)
  • Safety Issue:
  • Measure: Pharmacokinetics
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Pharmacokinetics
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Pharmacokinetics
  • Time Frame: 2 weeks (t1/2 will be assessed after the first two doses of IMCnyeso, an average of 2 weeks)
  • Safety Issue:
  • Measure: Pharmacokinetics
  • Time Frame: up to 2 years
  • Safety Issue:

Estimated Enrollment: 63

Study Start Date: May 1, 2018

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Male or female patients age ≥ 18 years of age at the time of informed consent
  2. HLA-A*0201 positive, confirmed by central laboratory
  3. NY-ESO-1 and/or LAGE-1A positive tumor confirmed by the central laboratory
  4. Arm 1: Patients must be refractory to or intolerant to all existing therapies known to provide clinical benefit for their condition.
  5. Arm 2: Subjects will have received the following previous therapies:
  6. NSCLC — PD-1/PD-L1 inhibitor
  7. Patients with NSCLC and an EGFR or ALK genomic tumor aberration must have disease progression after treatment with Health Authority-approved agents for these aberrations
  8. Urothelial cancer — PD-1/PD-L1 inhibitor
  9. Synovial sarcoma — at least one prior chemotherapy regimen
  10. Arm 1 only: Histologically confirmed diagnosis of advanced NSCLC, melanoma, urothelial carcinoma, or synovial sarcoma
  11. Arm 2 only: Histologically confirmed diagnosis of advanced NSCLC, urothelial carcinoma, or synovial sarcoma
  12. Arm 2 only: Disease amenable to biopsy
  13. Arm 2 only: Measurable disease to RECIST v.1.1 criteria

Exclusion Criteria:

  1. Impaired baseline organ function as evaluated by out-of-range laboratory values
  2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies
  3. Clinically significant cardiac disease or impaired cardiac function
  4. Presence of symptomatic or untreated central nervous system (CNS) metastases
  5. Active infection requiring systemic antibiotic therapy
  6. Known history of human immunodeficiency virus infection (HIV)
  7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  8. Malignant disease, other than that being treated in this study
  9. Patients receiving systemic steroid therapy or any other systemic immunosuppressive medication. Local steroid therapies are acceptable
  10. Systemic anti-cancer therapy within 2 weeks of the first dose of study drug.
  11. Major surgery within 2 weeks of the first dose of study drug
  12. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field
  13. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM-CSF, M-CSF) ≤ 2 weeks prior to start of study drug
  14. Pregnant, likely to become pregnant, or lactating women

Contact:

  • Rachael Easton, MD, PhD
  • 484-534-5261

Locations:

  • Thomas Jefferson University Hospital
  • Philadelphia Pennsylvania 19107 United States
  • Hillman Cancer Center
  • Pittsburgh Pennsylvania 15232 United States
  • The Christie Hospital
  • Manchester United Kingdom
  • Royal Marsden
  • Sutton United Kingdom

View trial on ClinicalTrials.gov


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Avelumab as Neoadjuvant Therapy in Subjects With Urothelial Muscle Invasive Bladder Cancers


Condition: Non-metastatic Muscle Invasive Bladder Cancer

Intervention:

  • Drug: Avelumab
  • Procedure: cystectomy
  • Combination Product: CG
  • Combination Product: DD-MVAC
  • Combination Product: PG

Purpose: Open-label, interventional, multi-centre, randomized phase II study. Cancer studied is non-metastatic muscle invasive bladder cancer (MIBC). Avelumab administered every 2 weeks is used as neoadjuvant therapy in subjects with urothelial muscle invasive bladder cancers in combination with standard chemotherapy or alone.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03674424

Sponsor: Jules Bordet Institute

Primary Outcome Measures:

  • Measure: Pathologic Complete Response
  • Time Frame: up to 3 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: To determine the pathologic response rate (
  • Time Frame: up to 3 months
  • Safety Issue:
  • Measure: To assess Toxicity Profile using the adverse events reported during the study
  • Time Frame: all along the study
  • Safety Issue:

Estimated Enrollment: 196

Study Start Date: June 1, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • 1. Age ≥ 18 years old 2. Must have histologically confirmed muscle invasive urothelial carcinoma (transitional cell carcinoma) or urothelial carcinoma with mixed histology of the bladder, renal pelvis or ureters. Stage permitted: T2, T3 or T4a. T stage is based on the standard of care transurethral resection of the bladder tumour (TURBT) sample 3. Patients may have nodal disease (Nx, N0, N1 or N2) at imagery but there must be no evidence of distant metastases 4. Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG). In addition in the cisplatin-ineligible cohort. Performance status 2 could be included. 5. Be a medically appropriate candidate for surgery as determined by an attending urologist 6. Adequate bone marrow function as defined below
  • Absolute neutrophil count ≥1500/µL or 1.5x109/L
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥100000/µL or 100x10 9/L 7. Adequate liver function as defined below
  • Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome < 3xUNL is allowed
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN 8. Serum pregnancy test (for subjects of childbearing potential) negative within 7 days prior to study treatment administration. 9. Women of childbearing potential must agree to use one highly effective method of contraception prior study entry, during the course of the study and up to 6 months after the last administration of study treatment. Men with childbearing potential partner must agree to use condom during the course of this study and up to 6 months after the last administration of the study treatment. 10. Completion of all necessary screening procedures within 28 days prior to treatment. 11. Availability of biological material for screening and/or translational research activities 12. Signed Informed Consent form (ICF) obtained prior to any study related procedure. Cisplatin-eligible cohort specific criteria: 13. Glomerular filtration rate (GFR) or Creatinine Clearance≥ 60 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) 14. Peripheral neuropathy ≤ grade 1 15. Hearing impaired ≤ grade 1 16. Adequate cardiac function (Left Ventricular Ejection Fraction LVEF ≥ 55%) by MUGA (Multiple-Gated Acquisition) scan or echocardiography Cisplatin ineligible cohort specific criteria (if any of the following criteria): 17. Glomerular filtration rate (GFR) or Creatinine Clearance ≥ 30mL/min according to the Cockcroft-Gault formula (or local institutional standard method) or 18. Peripheral neuropathy grade 2 or 19. Hearing impaired grade 2

Exclusion Criteria:

  1. Metastatic disease (M1)
  2. Has had prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for urothelial carcinoma
  3. Prior treatment with drug specifically targeting T-cell co-stimulation or checkpoint pathways
  4. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  5. Has an active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  6. Has had a prior organ transplantation including allogenic stem-cell transplantation.
  7. Has an active infection requiring systemic therapy
  8. Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome.
  9. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected)
  10. Has received vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines such as influenza vaccine.
  11. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 28 days prior to study registration
  12. History of prior invasive malignancy within 2 years (exception of adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal carcinoma in situ)
  13. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
  14. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication."
  15. Pregnant and/or lactating women.
  16. Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
  17. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade >1); however, alopecia, sensory neuropathy Grade ≤2, or other Grade ≤2 not constituting a safety risk based on investigator's judgment are acceptable.
  18. Other severe acute chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with the study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Locations:

  • Institut Jules Bordet
  • Brussels 1000 Belgium
  • CHU de Liège Sart Tilman
  • Liège 4000 Belgium
  • CHU Namur - Sainte Elisabeth
  • Namur 5000 Belgium

View trial on ClinicalTrials.gov


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A Multicenter Randomized Double Blind Study Examining the Efficacy and Safety of Denosumab in Combination With First Line Platinum-based Chemotherapy for Patients With Bone Metastasis Secondary to Metastatic Urothelial Cancer


Condition: Urothelial Carcinoma, Kidney Cancer, Ureter Cancer, Bladder Cancer

Intervention:

  • Drug: Denosumab
  • Other: Denosumab Placebo
  • Drug: Gemcitabine
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Dietary Supplement: Calcium
  • Dietary Supplement: Vitamin D

Purpose: This is a phase 2 study of the drug denosumab for the management bone metastases from urothelial cancer. The purpose of this study is to find out how effective denosumab is in the management of bone metastases from urothelial cancer. This will be done by comparing denosumab with standard treatment, compared to placebo and standard treatment. Denosumab is a monoclonal antibody that binds to a protein called Receptor Activator of Nuclear Factor κB (RANK). RANK works by telling certain cells called osteoclasts to break down bone tissue. The binding of denosumab to RANK stops it from telling osteoclasts to break down bone tissue which may help with symptoms related bone metastases from urothelial cancer.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03520231

Sponsor: University Health Network, Toronto

Primary Outcome Measures:

  • Measure: Difference in mean percentage change in serum c-telopeptide (sCTX) between the two arms (investigational drug arm and placebo arm).
  • Time Frame: Baseline to Week 10
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Number of patients with a change in sCTx
  • Time Frame: Baseline to Week 10
  • Safety Issue:
  • Measure: Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the investigational arm
  • Time Frame: Baseline to Week 10
  • Safety Issue:
  • Measure: Mean percentage change in urinary N-telopeptide (uNTx) levels in the investigational arm
  • Time Frame: Baseline to Week 10
  • Safety Issue:
  • Measure: Mean percentage change in sCTx levels in the investigational arm
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Mean percentage change in bALP levels in the investigational arm
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Mean percentage change in uNTx levels in the investigational arm
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the placebo arm.
  • Time Frame: Baseline to Week 10
  • Safety Issue:
  • Measure: Mean percentage change in urinary N-telopeptide (uNTx) levels in the placebo arm.
  • Time Frame: Baseline to Week 10
  • Safety Issue:
  • Measure: Mean percentage change in sCTx levels in the levels in the placebo arm.
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Mean percentage change in bALP levels in the levels in the placebo arm.
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Mean percentage change in uNTx levels in the levels in the placebo arm.
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Time to first on study symptomatic skeletal related events
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Progression free survival rate
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Progression free survival rate
  • Time Frame: 18 months
  • Safety Issue:
  • Measure: Overall survival rate
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Overall survival rate
  • Time Frame: 18 months
  • Safety Issue:
  • Measure: Number of participants with side effects in the investigational drug arm
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Number of participants with side effects in the placebo arm
  • Time Frame: 2 years
  • Safety Issue:

Estimated Enrollment: 50

Study Start Date: September 4, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Histologically or cytologically confirmed urothelial carcinoma (kidney, ureter, bladder) with metastatic disease involving the bones, not amenable to curative treatment
  • Mixed histologies permitted as long as urothelial histology is the major component Presence of one or more bone metastases
  • No prior systemic chemotherapy for metastatic disease (immunotherapy permitted)
  • Starting first line chemotherapy for metastatic urothelial cancer with gemcitabine and cisplatin or gemcitabine and carboplatin and planned to receive 4-6 cycles
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Adequate renal function
  • Acceptable serum calcium or albumin-adjusted serum calcium
  • Adequate hepatic function
  • Patients all require oral examination and appropriate preventative dentistry prior to starting treatment
  • Expected life expectancy of at least 3 months

Exclusion Criteria:

  • Prior chemotherapy for metastatic disease
  • Current or prior IV bisphosphonate or denosumab administration
  • Current or prior oral bisphosphonate administration to treat bone metastases
  • Unacceptable renal function
  • Abnormal bone metabolism (Paget's disease)
  • Untreated or symptomatic brain metastases
  • Patients with a history of other malignancies, with exceptions
  • Significant dental/oral disease
  • Administration of other prior anticancer therapies within 2 weeks of randomization
  • Patient is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment
  • Female of child bearing potential is not willing to use, in combination with her partner, highly effective contraception during treatment and for 7 months after the end of treatment
  • Known sensitivity to any of the products to be administered during the study
  • History of any other clinically significant disorder, condition or disease that in the opinion of the investigator excludes the patient

Contact:

  • Srikala Sridhar, M.D.
  • 416-946-4501 Ext. 2662

Location:

  • Princess Margaret Cancer Centre
  • Toronto Ontario M5G 2M9 Canada

View trial on ClinicalTrials.gov


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Cabozantinib Plus Pembrolizumab as First-Line Therapy for Cisplatin-Ineligible Advanced Urothelial Carcinoma (PemCab)


Condition: Metastatic Urothelial Carcinoma, Bladder Cancer

Intervention:

  • Drug: Cabozantinib
  • Drug: Pembrolizumab

Purpose: This is an open label, non-randomized phase 2 study of the combination of pembrolizumab and cabozantinib to assess overall response rate (ORR), progression free survival at 6 months (PFS6), and overall survival (OS) in patients with metastatic urothelial carcinoma (UC) ineligible for cisplatin.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03534804

Sponsor: University of Utah

Primary Outcome Measures:

  • Measure: Overall Response Rate (ORR)
  • Time Frame: 12 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression-free survival (PFS) at 6 months (PFS6)
  • Time Frame: 6 months
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: Patients are expected to stay on treatment for approximately 12 months; 18 months
  • Safety Issue:
  • Measure: Occurrence of Adverse Events and Serious Adverse Events
  • Time Frame: 12 months
  • Safety Issue:

Estimated Enrollment: 39

Study Start Date: September 18, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Eligibility Criteria:

  1. for consideration of treatment with immunotherapy using a checkpoint inhibitor following surgical resection. Treatment

Inclusion Criteria:

  • Histologically proven muscle-invasive transitional cell or urothelial carcinoma.
  • Metastatic (any N+ or M1) or locally advanced, unresectable (T4bN0) disease.
  • Measurable disease is required as determined by RECIST v1.1.
  • Performance Status ECOG 0-2
  • Cisplatin-ineligibility based on ≥1 of the following:
  • Estimated creatinine clearance between ≥30 and <60 ml/min (Cockcroft-Gault formula)
  • ECOG PS>1
  • Hearing loss
  • Baseline neuropathy > grade 1.
  • Patient refusal
  • Be greater to or equal to 18 years of age on day of signing informed consent.
  • Adequate organ function as defined in the protocol
  • Serum albumin ≥ 2.8 g/dl
  • Alkaline phosphatase (ALP) ≤ 3 × upper limit of normal (ULN). ALP ≤ 5 × ULN with documented bone metastases.
  • Negative serum or urine pregnancy test at screening for women of childbearing potential.
  • Highly effective contraception for both male and female subjects throughout the study and for at least 120 days after last pembrolizumab treatment administration if the risk of conception exists.
  • Must have recovered from adverse effects of any prior surgery, radiotherapy or other antineoplastic therapy.
  • Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. Alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
  • Last dose of any radiation therapy ≥ 2 weeks before first dose of study treatment.
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

  • Previous systemic chemotherapy treatment for urothelial carcinoma, with the exception of perioperative chemotherapy treatment alone or with concurrent radiation within 6 months prior to treatment.
  • Small-cell or sarcomatoid component in histology
  • Has received prior treatment with cabozantinib.
  • Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
  • Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or other checkpoint inhibitors in the adjuvant setting.
  • Radiation therapy for bone metastasis ≤ 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
  • Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
  • Low-dose low molecular weight heparins (LMWH) are permitted.
  • Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  • The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 × ULN within 7 days before the first dose of study treatment.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Ongoing congestive heart failure exacerbation or New York Heart Association Class 4, unstable angina pectoris, serious cardiac arrhythmias.
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.
  • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
  • Class 3 congestive heart failure
  • Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
  • The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
  • Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose.
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
  • Lesions invading or encasing any major blood vessels.
  • Other clinically significant disorders that would preclude safe study participation.
  • Serious non-healing wound/ulcer/bone fracture.
  • Uncompensated/symptomatic hypothyroidism.
  • Moderate to severe hepatic impairment (Child-Pugh B or C).
  • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment. Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
  • Diagnosis of another malignancy within 2 years before first dose of study treatment, with the exception of those determined by the treating investigator to have a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated surgically with curative intent, localized prostate cancer treated with curative intent and/or no intent for further treatment, or incidental prostate cancer)
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, intranasal, inhaled, topical steroids, or local steroid injection) is not considered an exclusion.
  • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent per treating physician's clinical judgment. Subjects with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  • Prior organ transplantation including allogenic stem-cell transplantation.
  • Has known history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Active and inactive vaccinations within 4 weeks of the first dose of pembrolizumab and while on trial is prohibited.
  • Known prior severe hypersensitivity to investigational products or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Subjects taking prohibited medications as described in Section 6.8. A washout period of prohibited medications for a period of at least two weeks or as clinically indicated should occur prior to the start of treatment.
  • Inability to swallow tablets or evidence of impaired intestinal absorption Previous systemic chemotherapy treatment for urothelial carcinoma, with the exception of perioperative chemotherapy treatment alone or with concurrent radiation within 6 months prior to treatment.

Contact:

  • Jill Broghammer
  • 801-213-6232

Location:

  • Huntsman Cancer Institute
  • Salt Lake City Utah 84112 United States

View trial on ClinicalTrials.gov


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A Pilot Study to Evaluate the Safety of Neoadjuvant Nivolumab Alone or in Combination With Ipilimumab for Cisplatin-Ineligible Patients With Muscle Invasive Bladder Cancer (CA209-9DJ)


Condition: Bladder Cancer

Intervention:

  • Drug: Nivolumab
  • Drug: Ipilimumab
  • Procedure: Radical cystectomy

Purpose: The purpose of this study is to test if immunotherapy with nivolumab alone or in combination with ipilimumab is safe and does not delay the planned bladder cancer surgery. The investigators want to see if treatment with these drugs prior to surgery may decrease the size of the bladder cancer and thus could help make the surgery more successful.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03520491

Sponsor: Memorial Sloan Kettering Cancer Center

Primary Outcome Measures:

  • Measure: number of patients who proceed to radical cystectomy and pelvic lymph node dissection
  • Time Frame: within 60 days after completion of neoadjuvant nivolumab or nivolumab in combination with ipilimumab
  • Safety Issue:

Estimated Enrollment: 45

Study Start Date: April 25, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant histology is acceptable if there is a predominant urothelial component.
  • Cystoscopically and radiographically confirmed cT2-4a cN0 cM0 disease. Patients with cT4a disease invading into the prostatic stroma with no cystoscopic confirmation of muscle invasion are eligible.
  • Patients ineligible for cisplatin based on any of the following criteria:
  • Estimated or calculated creatinine clearance ≥ 30ml/min but < 60 ml/min
  • Grade 2 or above audiometric hearing loss (per CTCAE v4.0)
  • Grade 2 or above peripheral neuropathy (per CTCAE v4.0)
  • Availability of tumor specimen block or 30 unstained slides from diagnosis of muscle-invasive disease. Patients with fewer than 30 slides available may be enrolled after discussion with the Principal Investigator.
  • Karnofsky performance status ≥ 70%.
  • Age ≥ 18 years.
  • Required initial laboratory values:
  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Bilirubin ≤1.5 times the upper limit of normal (x ULN)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
  • PTT/PT ≤1.5 x ULN or INR < 1.7 x ULN for patients who are not receiving therapeutic anticoagulation. Patients receiving therapeutic anticoagulation should be on a stable dose.

Exclusion Criteria:

  • Prior treatment with systemic chemotherapy for bladder cancer. (Prior intravesical treatment is allowed.)
  • Prior bladder-directed radiotherapy.
  • Presence of active autoimmune disease, symptoms, or conditions, with the following exceptions: °Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, asymptomatic laboratory evidence of autoimmune disease (e.g.: +ANA, +RF, anti-thyroglobulin antibodies), or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first dose of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease.
  • Unstable angina.
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure.
  • History of myocardial infarction within 6 months.
  • History of stroke within 6 months.
  • Evidence of bleeding diathesis or coagulopathy. Therapeutic anticoagulation is permitted, but patients must be on a stable dose.
  • Major surgical procedure within 28 days prior to the study.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Other prior malignancy active within the previous 2 years except for local or organ-confined early stage cancer that has been definitively treated with curative intent or does not require treatment, does not require ongoing treatment, has no evidence of active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the endpoints of the study.
  • Subjects who have received prior therapy with any T cell co-stimulation or checkpoint pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137; or other medicines specifically targeting T cells are prohibited. Prior IL-2 is permitted.
  • Prior therapy with intravesical BCG within 6 weeks of treatment.
  • Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • History of allergy to study drug component or history of severe hypersensitivity reaction to any monoclonal antibody.
  • Women who are breastfeeding or pregnant as evidenced by a positive pregnancy test within 14 days of first dose.
  • Male subjects who are unwilling to use contraception during the treatment and for at least 31 weeks after the last dose of study treatment (5 half-lives of study drug plus 90 days duration of sperm turnover).
  • Women of childbearing potential (WOCBP) not using a medically acceptable means of contraception throughout the study treatment and for at least 23 weeks following the last dose of study treatment (5 half-lives of study drug plus 30 days duration of ovulatory cycle).
  • WOCBP are defined as those who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post-menopausal is defined as:
  • Amenorrhea ≥ 12 consecutive months without another cause, or
  • For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
  • Inability to comply with study and/or follow-up procedures.

Contact:

  • Min Yuen Teo, MB BCh
  • 914-367-7393

Locations:

  • Memoral Sloan Kettering Basking Ridge
  • Basking Ridge New Jersey 07920 United States
  • Memorial Sloan Kettering Westchester
  • Harrison New York 10604 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States

View trial on ClinicalTrials.gov


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Phase I Study of MK-3475 in Combination With BCG for Patients With High Risk Superficial Bladder Cancer


Condition: Bladder Cancer

Intervention:

  • Drug: Intravenous MK-3475/ Intravesical BCG

Purpose: This is a single center Phase I safety and efficacy study of MK-3475 therapy used in combination with bladder infused BCG treatment for patients, 18 years or older, with high risk superficial bladder cancer (cancer not yet involving the muscle of the bladder wall) who have had removal of their bladder tumor. Patients will be enrolled to a single treatment group of a fixed dose of MK 3475 and BCG.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02324582

Sponsor: Southern Illinois University

Primary Outcome Measures:

  • Measure: safety (Grade and quantity of adverse events)
  • Time Frame: change from baseline to 23 weeks
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Complete Response Rate (cytoscopy)
  • Time Frame: change from baseline to 19 weeks; 3, 12, and 24 months post treatment completion
  • Safety Issue:
  • Measure: Change in Quality of Life
  • Time Frame: change from baseline to 10 weeks, 19 weeks and 3, 12, and 24 months post-Week 19 cystectomy
  • Safety Issue:
  • Measure: Change in Quality of Life
  • Time Frame: change from baseline to 10 weeks, 19 weeks and 3, 12, and 24 months post-Week 19 cystectomy
  • Safety Issue:

Estimated Enrollment: 15

Study Start Date: June 2015

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. 1.Willing and able to provide written informed consent/assent. 2.18 years of age. 3.Have pathologically documented high grade transitional cell superficial bladder cancer (Ta, T1) at time of restaging, or have pathologically documented high grade CIS of the bladder at time of initial resection for recurrent/persistent high risk transitional cell superficial bladder cancer. 4.Recurrent/persistent disease despite 2 Induction Intravesical Therapy Courses given within 12 months (with BCG being one of them), or despite one induction BCG treatment in addition to at least one maintenance course of BCG 5.Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion. 6.ECOG performance status of 0-
  2. 7.Demonstrate adequate organ function 8.Female subject of childbearing potential should have a negative urine or serum pregnancy. 9.Female subjects of childbearing potential should be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication 10.Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

  1. Currently has active or progressive metastatic disease.
  2. Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
  3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  4. Prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  5. Prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for bladder cancer.
  6. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  7. Known additional malignancy that is progressing or requires active treatment.
  8. Active autoimmune disease that has required systemic treatment in past 2 years.
  9. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  10. Active infection, including a concurrent febrile illness, requiring systemic therapy.
  11. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  12. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 4 months after the last dose of trial treatment.
  14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) including anti-CD40 and anti-OX40 antibodies.
  15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  16. Has known active Hepatitis B (e.g., HBs Ag reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  17. Has known active tuberculosis. Subjects will not be specifically tested for the study; however, subjects that are tested within 28 days of beginning study or while on study and test positive with the PPD test before treatment should have active tuberculosis ruled out before therapy begins for their superficial bladder cancer.
  18. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
  19. Has an active urinary tract infection, gross hematuria, or known broken mucosal barrier of the bladder.
  20. Less than 14 days post bladder biopsy, TUR, or traumatic catheterization.
  21. Evidence of muscle invasive bladder cancer, or transitional cell carcinoma of the upper urinary tract

Contact:

  • Sherjeel Sana, MD
  • 217-545-7969

Locations:

  • Simmons Cancer Institute-SIU School of Medicine
  • Springfield Illinois 62702 United States
  • Southern Illinois University School of Medicine
  • Springfield Illinois 62702 United States

View trial on ClinicalTrials.gov


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Phase 1B Study to Assess Safety and Efficacy of Neo-Adjuvant Bladder Urothelial Carcinoma COmbination-immunotherapy (NABUCCO)


Condition: Urothelial Carcinoma

Intervention:

  • Drug: Ipilimumab
  • Drug: Nivolumab

Purpose: In this single-arm trial we will investigate the safety of short-term preoperative therapy with ipilimumab and nivolumab in patients with high-risk resectable urothelial cancer. We will determine the number of patients that have surgical resection <12 weeks from first infusion, as this is an endpoint that is clinically meaningful for this population. 24 patients will be included. All patients will be receiving a sequenced scheme of Nivolumab and Ipilimumab.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03387761

Sponsor: The Netherlands Cancer Institute

Primary Outcome Measures:

  • Measure: Number of patients that have surgical resection <12 weeks after study start
  • Time Frame: At 12 weeks
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Efficacy of immunotherapy, assessed by by the percentage of pathological complete response rate (pCR) at cystectomy
  • Time Frame: At 12 weeks
  • Safety Issue:
  • Measure: Differences in immune infiltrates in responders vs nonresponders
  • Time Frame: At 12 weeks
  • Safety Issue:
  • Measure: T-cell (dys)functionality as measured by comparing the transcriptome of tumor-specific T cells in intra-patient pre- and post therapy tissue
  • Time Frame: At 12 weeks
  • Safety Issue:
  • Measure: Explore whether radiomics-based predictive models can be established for immunotherapy responders vs non-responders
  • Time Frame: at 12 weeks
  • Safety Issue:

Estimated Enrollment: 24

Study Start Date: January 15, 2018

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Willing and able to provide informed consent
  2. Age ≥ 18 years
  3. High-risk resectable urothelial cancer (upper urinary tract allowed) defined as stage III UC: cT3-4aN0M0 OR cT1-4aN1-3M0
  4. Refusal of neoadjuvant/induction cisplatin-based chemotherapy or patients in whom neoadjuvant cisplatin based therapy is not appropriate.
  5. World Health Organization (WHO) performance Status 0 or
  6. Urothelial cancer is the dominant histology (>70%).
  7. Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available
  8. Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.0x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, GFR>30 ml/min, AST ≤ 2.5 x ULN, ALT ≤2.5 x ULN, Bilirubin ≤1.5 X ULN
  9. Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
  10. For female patients of childbearing potential to use a highly effecting form(s) of contraception (i.e. one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for 180 days after the last dose of immunotherapy Adequate contraceptive methods are: condom, sterilization, other barrier contraceptive measures preferably in combination with condoms, oral contraceptives, intra-uterine device.

Exclusion Criteria:

  1. Subjects with active autoimmune disease in the past 2 years. Patients with diabetes mellitus, properly controlled hypothyroidism or hyperthyroidism, vitiligo, psoriasis or other mild skin disease can still be included.
  2. Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis).
  3. Prior CTLA-4 or PD-1/PD-L1-targeting immunotherapy.
  4. Known history of Human Immunodeficiency Virus, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA), active tuberculosis, or other active infection requiring therapy at the time of inclusion.
  5. Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events
  6. Medical condition requiring the use of immunosuppressive medications, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) will be allowed.
  7. Use of other investigational drugs before study drug administration
  8. Malignancy, other than urothelial cancer, in the previous 2 years, with a high chance of recurrence (estimated >10%). Patients with low risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
  9. Pregnant and lactating female patients.
  10. Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
  11. Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
  12. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
  13. Previous intravenous chemotherapy for bladder cancer. Prior chemoradiation is allowed.
  14. Patients in whom use of a colon segment for urinary diversion is planned

Contact:

  • Michiel MS van der Heijden, Dr.
  • +3120 512 9111

Location:

  • Antoni van Leeuwenhoek ziekenhuis
  • Amsterdam NH 1066CX Netherlands

View trial on ClinicalTrials.gov


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