Bladder Cancer

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Functional Imaging of T-Cell Activation With [18F]F-AraG in Urothelial Carcinoma Patients Receiving Neoadjuvant Therapy or Patients With Cancer Receiving Standard of Care Anti-PD-1/L1


Condition: Bladder Cancer

Intervention:

  • Drug: Fluorine F 18 Ara-G
  • Procedure: Positron Emission Tomography
  • Procedure: Magnetic Resonance Imaging

Purpose: This phase II trial studies how well fluorine F 18 Ara-G positron emission tomography (PET)/magnetic resonance (MR) imaging works in measuring clinical response to atezolizumab or patients with cancer receiving standard of care Anti-PD-1/L1. Diagnostic procedures, such as fluorine F 18 Ara-G PET/MR imaging, may help measure a patient's response to standard of care atezolizumab or Anti-PD-1/L1 treatment.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03007719

Sponsor: Lawrence Fong

Primary Outcome Measures:

  • Measure: The change between pre-treatment and post-treatment SUVmax (Standardized Uptake Values) in the primary and/or metastatic tumor(s) on whole-body [18F]F-AraG PET/MR (Positron Emission Tomography/Magnetic Resonance) imaging.
  • Time Frame: Baseline up to day 8
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Change in maximum standard uptake value (SUVmax)
  • Time Frame: Baseline up to day 8
  • Safety Issue:
  • Measure: The change between pre-treatment and post-treatment SUVmax in lymphoid organs on whole-body [18F]F-AraG PET/MR imaging (Cohort 1 and 2).
  • Time Frame: Baseline up to 8 days
  • Safety Issue:

Estimated Enrollment: 31

Study Start Date: March 7, 2017

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically or cytologically documented cancer to which anti-PD1 or anti-PDL1 are approved therapies
  • Eligible for with plan to undergo neoadjuvant treatment with atezolizumab followed by surgery as part of a companion study (NCT02451423), or planned to undergo treatment with anti-PD-1 or anti-PD-L1 per standard of care
  • Must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 regardless of disease stage (e.g. localized, locally advanced, or metastatic)
  • In female patients, negative pregnancy test with no plans to become pregnant during the duration of the study
  • Able to provide informed consent and follow the study guidelines
  • Archival tumor tissue from biopsy or resection will be required for all patients; archival tissue should be of good quality based on total and viable tumor contents; fine needle aspiration, brushing, and cytologic cell pellets are not acceptable

Exclusion Criteria:

  • History of prior treatment with immune checkpoint antibodies (e.g. anti-PD1, anti-PDL1, anti-CTLA4 antibody) or co-stimulatory agonist antibodies (e.g. anti-41BB, anti-OX40) * Prior intravesical treatment with Bacillus Calmette-Guerin (BCG) is allowed; however, the last dose must be at least 6 weeks from time of enrollment and patients must have documented progressive disease at least 6 weeks from completion of last BCG
  • Diagnosis of immunodeficiency including history of human immunodeficiency virus (HIV)
  • Receiving systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to first injection of [18F]F-AraG * Topical and inhaled corticosteroids are allowed
  • Prior allogeneic stem cell or solid organ transplant
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Biopsy or resection of the primary tumor within 14 days the first injection of [18F]F-AraG
  • Contraindication to magnetic resonance (MRI) imaging, as determined through review of the University of California, San Francisco (UCSF) MRI screening form by study investigator
  • Evidence of active infection within 14 days of study enrollment
  • Female patients who are pregnant or breastfeeding
  • Inability to receive furosemide (Lasix) in the opinion of the treating investigator
  • Patients that plan to receive off-label use of anti-PD1 or anti-PDL1

Contact:

  • Julie McCluggage, RN
  • 877-827-3222

Location:

  • University of California, San Francisco
  • San Francisco California 94158 United States

View trial on ClinicalTrials.gov


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Phase II Study of Adjuvant 3D-Conformal Radiotherapy in High Risk Bladder Cancer


Condition: Bladder Cancer, Squamous Cell Carcinoma of the Bladder, Stage III Bladder Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder

Intervention:

  • Radiation: 3D conformal radiation therapy

Purpose: This phase II trial studies how well modern, conformal radiation therapy after surgery works in treating patients with high-risk bladder cancer. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01954173

Sponsor: Emory University

Primary Outcome Measures:

  • Measure: Gastrointestinal (GI) late effects, assessed using Radiation Therapy Oncology Group (RTOG) Late Effects in Normal Tissues (LENT)/Subjective, Objective, Management and Analytic (SOMA) scales
  • Time Frame: 3 months to 10 yrs
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Acute adverse events greater than grade 2, graded by CTCAE version 4.0
  • Time Frame: Up to 90 days
  • Safety Issue:
  • Measure: Loco-regional failure, considered any failure in the treatment field of the pelvis
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Rate of distant metastases
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Rate of disease-free survival
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Overall survival rate
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Quality of life, assessed using FACT-BL
  • Time Frame: Up to 5 years
  • Safety Issue:

Estimated Enrollment: 41

Study Start Date: July 2013

Eligibility:

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

Inclusion Criteria:

  • Pathologic diagnosis of urothelial or squamous cell carcinoma of the bladder
  • Patients must have undergone cystectomy (total cystectomy, radical cystectomy +/- pelvic lymph node dissection) with no evidence of macroscopic residual disease
  • Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-2
  • Patients treated with simple cystectomy with macroscopically negative margins are eligible for this study
  • Clinical T-stage (prior to systemic therapy, if applicable) ≥ T3a and/or positive lymph nodes by transurethral resection of bladder tumor (TURBT)/magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET)-CT or pathologic T-stage ≥ T3a and/or positive lymph nodes

Exclusion Criteria:

  • Patients with metastatic disease outside of the pelvis
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
  • Prior radiation therapy to the pelvis
  • Patients with active inflammatory bowel disease
  • Severe acute co-morbidity, defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be significantly immunosuppressive; protocol-specific requirements may also exclude immunocompromised patients

Contact:

  • Joseph W Shelton, MD
  • 404-616-6343

Location:

  • Emory University Hospital/Winship Cancer Institute
  • Atlanta Georgia 30322 United States

View trial on ClinicalTrials.gov


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Pioglitazone and Risk of Bladder Cancer in Patients With Type 2 Diabetes Mellitus"PROBE-PIO"Study


Condition: Bladder Cancer

Intervention:

  • Drug: Pioglitazone

Purpose: Pioglitazone, an agonist of the peroxisome-proliferator-activated receptor (PPAR), is a relatively new oral anti-hyperglycemic drug. Since its first approval in the USA in 1999, a potential link with bladder cancer has been a subject of debate. US Food and Drug Administration (FDA) in September, 2010 and European Medicines Agency in July, 2011 issued an alert about a potential relation between the occurrence of bladder cancer and the prescription of pioglitazone, based on the data from various studies. France banned its use in July 2011. Recently Pioglitazone was banned from India without any evidence of increased bladder cancer in our population. With this background, we plan to study the risk of bladder cancer in male type 2 diabetes subjects aged more than 50 years who are on pioglitazone therapy as compared to never-users of pioglitazone in a retrospective cohort design and provide the first data from India to the policy makers regarding the purported risk in our ethnicity and geographical area.

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT01935466

Sponsor: Postgraduate Institute of Medical Education and Research

Primary Outcome Measures:

  • Measure: Bladder cancer rate
  • Time Frame: Prevalent bladder cancer on pioglitazone or anti diabetic drugs for 1 year
  • Safety Issue:

Estimated Enrollment: 6107

Study Start Date: July 2013

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Eligibility:

  • Age: minimum 50 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  1. Male Type 2 diabetes subjects with age >50 year
  2. On anti-diabetic drugs and/or insulin for≥ 1 year
  3. Patient willing to provide informed consent to be included in the study

Exclusion Criteria:

  • 1. Bladder cancer diagnosed before the onset of Diabetes mellitus. 2. Patient not willing to participate in the study.

Contact:

  • Ashu rastogi, MD, DM
  • 919781001046

Location:

  • Deptt of Endocrinology
  • Chandigarh 160012 India

View trial on ClinicalTrials.gov


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A Multicenter Study Evaluating Safety and Efficacy of TAR-200 in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Ineligible for or Refuse Cisplatin-based Chemotherapy and Who Are Unfit for Radical Cystectomy


Condition: Bladder Cancer TNM Staging Primary Tumor (T) T2A, Bladder Cancer TNM Staging Primary Tumor (T) T2B, Bladder Cancer TNM Staging Primary Tumor (T) T3A, Bladder Cancer TNM Staging Primary Tumor (T) T3B

Intervention:

  • Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03404791

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 as assessed by CTCAE V4.0
  • Time Frame: Study Day 0 to Study Day 84
  • Safety Issue:
  • Measure: Number of participants that do not require TAR-200 removal prior to the scheduled date of removal 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 84
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Proportion of subjects with clinical complete response (cCR)
  • Time Frame: Approximately Study Day 0 to Study Day 360
  • Safety Issue:
  • Measure: Proportion of subjects with clinical partial response (cPR)
  • Time Frame: Approximately Study Day 0 to Study Day 360
  • Safety Issue:
  • Measure: Proportion of subjects with stable disease (SD)
  • Time Frame: Approximately Study Day 0 to Study Day 360
  • Safety Issue:
  • Measure: Proportion of subjects with progression
  • Time Frame: Approximately Study Day 0 to Study Day 360
  • Safety Issue:
  • Measure: Symptom control
  • Time Frame: Approximately Study Day 0 to Study Day 360
  • Safety Issue:
  • Measure: Time to intervention for symptom control
  • Time Frame: Approximately Study Day 0 to Study Day 360
  • Safety Issue:
  • Measure: Time to progression
  • Time Frame: Approximately Study Day 0 to Study Day 360
  • Safety Issue:
  • Measure: Proportion of subjects undergoing post-treatment interventions by 3, 6, 9, and 12 months
  • Time Frame: Approximately Study Day 0 to Study Day 360
  • Safety Issue:
  • Measure: Proportion of subjects surviving at 12 months
  • Time Frame: Approximately Study Day 0 to Study Day 360
  • Safety Issue:

Estimated Enrollment: 30

Study Start Date: January 26, 2018

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  1. Histological proof of non-metastatic muscle-invasive urothelial cell carcinoma of the bladder.
  2. Subject must have been as fully resected as possible per the physician's judgment.
  3. Subjects must be deemed unfit for RC due to comorbid conditions with a risk of mortality.
  4. Subjects must refuse or be deemed ineligible for cisplatin-based chemotherapy.
  5. Subject must refuse or not be eligible for radiotherapy.
  6. Life expectancy of at least 4 months.
  7. Adequate bone marrow, liver, and renal function.
  8. Subjects must be willing to undergo a cystoscopy.
  9. Subjects must be willing to undergo a biopsy for assessment of clinical response.
  10. Written informed consent and authorization for release of personal health information obtained according to local laws.
  11. Age ≥18 years at the time of informed consent.
  12. Females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after treatment discontinuation. Subject's partner must also use barrier protection while subject is on study until 4 weeks after treatment discontinuation.
  13. Males must be willing to use an effective method of contraception/method to avoid seminal transfer (barrier method or abstinence) from the time consent is signed until 4 weeks after treatment discontinuation. Subject's partner must also use barrier protection while subject is on study until 4 weeks after treatment discontinuation.
  14. Females of childbearing potential must have a negative pregnancy test within 21 days prior to Study Day 0.

Exclusion Criteria:

  1. Other active malignancies.
  2. 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
  3. Pyeloureteral tube externalized to the skin (ureteral stent or unilateral nephrostomy tube is allowed).
  4. Evidence of bladder perforation during diagnostic cystoscopy.
  5. Bladder post-void residual volume (PVR) of >750 mL.
  6. Concurrent clinically significant infections as determined by the treating Investigator.
  7. Known hypersensitivity to gemcitabine (or other drug excipients) or chemically related drugs.
  8. Known hypersensitivity to the device constituent or TARIS Inserter materials.
  9. Use of an investigational product within 30 days or 5 half-lives, whichever is longer, preceding Study Day
  10. Female subject who is lactating/breastfeeding.
  11. Difficulty providing blood samples.
  12. Unwilling or unable to provide informed consent or comply with the requirements of this protocol, including the presence of any condition (physical, mental or social) that is likely to affect the subject's return for scheduled visits and follow-up.
  13. Other unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for enrollment.

Contact:

  • TARIS Biomedical LLC
  • +1-971-676-7750

Locations:

  • Mayo Clinic
  • Phoenix Arizona 85054 United States
  • Chesapeake Urology
  • Hanover Maryland 21076 United States
  • Michigan Institute of Urology
  • Troy Michigan 48084 United States
  • University of Rochester Medical Center
  • Rochester New York 14642 United States
  • Urology Associates of Nashville
  • Nashville Tennessee 37209 United States
  • Vanderbilt University Medical Center
  • Nashville Tennessee 37232 United States
  • North Austin Urology
  • Austin Texas 78750 United States
  • Urology of Virginia
  • Virginia Beach Virginia 23462 United States
  • Fundacion Puigvert
  • Barcelona Spain
  • Hospital Universitario 12 de Octubre
  • Madrid Spain
  • Instituto Valenciano de Oncologia
  • Valencia Spain

View trial on ClinicalTrials.gov


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A Phase II Study of Olaparib (AZD2281) in Patients With Metastatic/Advanced Urothelial Carcinoma With DNA-Repair Defects


Condition: ABL1 Gene Mutation, Abnormal DNA Repair, Advanced Urothelial Carcinoma, ATM Gene Mutation, ATR Gene Mutation, ATRX Gene Mutation, BAP1 Gene Mutation, BARD1 Gene Mutation, BLM Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation, BRD4 Gene Mutation, BRIP1 Gene Mutation, CCND1 Gene Mutation, CHEK1 Gene Mutation, CHEK2 Gene Mutation, DOT1L Gene Mutation, FANCC Gene Mutation, FANCD2 Gene Mutation, FANCE Gene Mutation, FANCF Gene Mutation, FANCG Gene Mutation, FANCL Gene Mutation, IKBKE Gene Mutation, MEN1 Gene Mutation, Metastatic Urothelial Carcinoma, MLH1 Gene Mutation, MSH2 Gene Mutation, MSH6 Gene Mutation, MUTYH Gene Mutation, NPM1 Gene Mutation, PALB2 Gene Mutation, PMS2 Gene Mutation, POLD1 Gene Mutation, POLE Gene Mutation, PRKDC Gene Mutation, RAD50 Gene Mutation, RAD51 Gene Mutation, SMARCB1 Gene Mutation, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage IV Bladder Urothelial Carcinoma AJCC v7, STK11 Gene Mutation

Intervention:

  • Drug: Olaparib

Purpose: This phase II trial studies how well olaparib works in treating patients with urothelial cancer with DNA-repair defects that has spread to other places in the body (advanced or metastatic) and usually cannot be cured or controlled with treatment. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03375307

Sponsor: National Cancer Institute (NCI)

Primary Outcome Measures:

  • Measure: Overall response rate (ORR) as evaluated by Response Evaluation Criteria in Solid Tumors (RECIST)
  • Time Frame: Up to 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression free survival (PFS)
  • Time Frame: From the date of olaparib initiation to investigator-assessed clinical progression or radiographic progression (by RECIST), or death from any cause, whichever occurs first, assessed up to 5 years
  • Safety Issue:
  • Measure: Incidence of adverse events
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Individual deoxyribonucleic acid (DNA)-repair defects
  • Time Frame: Up to 5 years
  • Safety Issue:

Estimated Enrollment: 150

Study Start Date: August 3, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the urothelial tract/bladder cancer
  • Patients must have Clinical Laboratory Improvement Act (CLIA) confirmed presence of a somatic or germline alteration considered pathogenic/likely pathogenic by FM and/or the Genetics Review Panel in one or more of the following genes: BRCA1, BRCA2, ATM, BAP1, FANCF, PALB2, and BRIP1 or in one or more of the DNA-repair genes tested in the FoundationOne FoundationOneCDx (F1CDx) panel including the following genes (Foundation One mutation analysis results and Foundation Liquid results performed prior to enrollment on this study may be accepted for eligibility review): ABL1, ATR, ATRX, BARD1, BLM, BRD4, CCND1, CHEK1, CHEK2, DOT1L, FANCC, FANCD2, FANCE, FANCG, FANCL, IKBKE, MEN1, MLH1, MSH2, MSH6, MUTYH, NPM1, PMS2, POLD1, POLE, PRKDC, RAD50, RAD51, SMARCB1, STK11
  • Note: FoundationOneCDx (F1CDx) is a next generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Evidence of disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) during treatment or after the most recent dose of therapy with at least one platinum-based regimen of chemotherapy and/or an immune-checkpoint inhibitor (atezolizumab, pembrolizumab, nivolumab, avelumab or durvalumab) (2-week washout from chemotherapy and 4-weeks washout from monoclonal antibodies is required)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (or Karnofsky >= 70%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (for subjects with documented Gilbert's disease total bilirubin =< 3.0 mg/dL)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (for subjects with liver metastasis AST/ALT =< 5 x ULN)
  • Creatinine clearance >= 50 mL/min/1.73 m^2
  • Hemoglobin >= 10 g/dL; transfusions are allowed
  • Prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT) within 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed
  • Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of olaparib
  • Pre-clinical data indicate that olaparib adversely affects embryofetal survival and development; therefore, women of child-bearing potential and their partners should agree to use two (2) highly effective forms of contraception throughout study participation and for at least one (1) month after the last dose of olaparib; male study participants should avoid fathering a child or donating sperm during the study and for three (3) months after the last dose of olaparib
  • Note: Olaparib is a PARP inhibitor with the potential for teratogenic or abortifacient effects; because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib, breastfeeding should be discontinued if the mother is treated with olaparib
  • Ability to understand and the willingness to sign a written informed consent document or patients with impaired decision making capacity (IDMC) if they are represented by a legally authorized representative (LAR)
  • Patients must provide tumor sample for mutation analysis or be willing to undergo mandatory screening biopsy
  • Patients must have a life expectancy >= 16 weeks
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1
  • Postmenopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  • Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50
  • Radiation-induced oophorectomy with last menses > 1 year ago
  • Chemotherapy-induced menopause with >1 year interval since last menses
  • Surgical sterilization (bilateral oophorectomy or hysterectomy)
  • Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations

Exclusion Criteria:

  • Patients with benign or variants of unknown significance as determined by FoundationOne FoundationOneCDx (F1CDx) panel and Genetics Review Panel review will be excluded
  • Patients who have had prior treatment with olaparib or any other PARP inhibitor (PARPi)
  • Patients with myelodysplastic syndrome/acute myeloid leukemia; or baseline features suggestive of myelodysplastic syndrome or acute myelogenous leukemia on peripheral blood smear or bone marrow biopsy, if clinically indicated
  • Persistent toxicities (>= Common Terminology Criteria for Adverse Events [CTCAE] grade 2) with the exception of alopecia, caused by previous cancer therapy
  • Patients who are receiving any other investigational agents; patients may be on other clinical trials or treatment during screening to determine eligibility
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; a scan to confirm the absence of brain metastases is not required; patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition of olaparib
  • Patients receiving any medications or substances that are inhibitors or inducers of CYP3A are ineligible; a washout period prior to starting olaparib for patients on CYP3A inhibitors is 2 weeks; and the required washout period for CYP3A inducers is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
  • Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference texts such as the Physicians' Desk Reference; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Pregnant women are excluded from this study because olaparib is a PARP inhibitor agent with the potential for teratogenic or abortifacient effects
  • Any chronic or concurrent acute liver disease
  • History of stroke, transient ischemic attack (TIA), or myocardial infarction, within 6 months prior to enrollment
  • Uncontrolled concurrent disease or illness including but not limited to:
  • Ongoing or active infection
  • Symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia
  • Unstable or untreated cardiac conditions or ejection fraction of < 50% as determined by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
  • Uncontrolled diabetes mellitus
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
  • Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
  • Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma, or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for >= 5 years; patients with a history of localized triple negative breast cancer or localized resected prostate cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
  • Resting electrocardiogram (ECG) with corrected QT (QTc) > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment
  • Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)

Locations:

  • Los Angeles County-USC Medical Center
  • Los Angeles California 90033 United States
  • USC / Norris Comprehensive Cancer Center
  • Los Angeles California 90033 United States
  • USC Norris Oncology/Hematology-Newport Beach
  • Newport Beach California 92663 United States
  • University of Colorado Hospital
  • Aurora Colorado 80045 United States
  • University of Kentucky/Markey Cancer Center
  • Lexington Kentucky 40536 United States
  • NCI - Center for Cancer Research
  • Bethesda Maryland 20892 United States

View trial on ClinicalTrials.gov


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A Phase II Trial of Transurethral Surgery Followed by a Combination of Atezolizumab (Tecentriq™) an Anti-PDL-1 (MPDL3280A) With Trimodal Therapy in Patients With Muscle-Invasive Bladder Cancer


Condition: Safety Issues

Intervention:

  • Drug: Atezolizumab

Purpose: This is a single arm phase II trial to (1) evaluate safety and toxicity profile of intravenous Atezolizumab (anti-PDL-1) administered in combination with TMT in patients with MIBC, (2) To determine the loco-regional control rate (LCR) of TMT combined with PDL-1 blockade.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03620435

Sponsor: McGill University Health Center

Primary Outcome Measures:

  • Measure: Safety profile of intravenous Atezolizumab (anti-PDL-1) administered in combination with TMT in patients with MIBC
  • Time Frame: 2-2.5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Overall survival
  • Time Frame: 4 years
  • Safety Issue:
  • Measure: Bladder cancer therapy impact on quality of life
  • Time Frame: 2-2.5 years
  • Safety Issue:
  • Measure: Complete response to TMT combined with PDL-1 blockade
  • Time Frame: 2-2.5 years
  • Safety Issue:

Estimated Enrollment: 25

Study Start Date: May 1, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • 18 years old or older
  • Histologic diagnosis of urothelial carcinoma of the bladder. Focal differentiation allowed other than small cell histology.
  • Stage T2-T4a N0M0 (AJCC-TNM version 6) based on trans-urethral resection of bladder tumor (TURBT), CT imaging, +/- bimanual examination under anaesthesia (EUA).
  • CT scan of chest/abdomen/pelvis within 8 weeks from the start of treatments, showing no evidence of metastatic disease.
  • Attempt of complete TURBT within 56 days (8 weeks) prior to the start of chemoradiation. If TURBT was performed > 8 weeks ago but a recent cystoscopy show no residual disease, then a repeat TURBT is not necessary.
  • Life Expectancy greater than 6 months
  • ECOG performance status of 2 or better
  • Another primary cancer is allowed only if treated with curative intent at least 3 years prior to enrollment without evidence of recurrence or if the untreated cancer is clinical indolent (eg lower risk prostate cancer).
  • Adequate hematologic reserve: Platelet count ≥ 150,000/ul, WBC ≥ 4000/ul. Anemia will be corrected to minimum hemoglobin of 100 g/L with red cell transfusions, if necessary.
  • Adequate liver function with a bilirubin ≤ 1.5 ULN[27] and SGOT/SGPT < 1.5 X the upper normal limit
  • Patients must be considered able to tolerate systemic chemosensitizer combined with pelvic IMRT by the joint agreement of the participating radiation oncologist and medical oncologist.
  • Able and willing to give written informed consent.

Exclusion Criteria:

  • Prior systemic therapy for other urothelial tumors. Neoadjuvant chemotherapy can be considered a component of the trimodal therapy and is allowed. Superficial bladder treatments including BCG and mitomycin C are permitted if completed 6 weeks prior to therapy.
  • Hypersensitive to Gemcitabine or to any ingredient in the formulation or component of the container.
  • Prior RT to the pelvis
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug, whichever is longer, prior to enrollment
  • Malignancies other than urothelial cancer within 5 years prior to Cycle 1, Day 1: Patients with localized lower risk prostate cancer (defined as Stage ≤T2b, Gleason score ≤ 7, and PSA at prostate cancer diagnosis ≤ 20 ng/mL[if measured]) treated with radical prostatectomy and without prostate-specific antigen (PSA) recurrence are eligible. Patients with lower risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 7 and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible. Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of metastasis or death <5% at 5 years) are eligible provided they meet all of the following criteria: Malignancy treated with expected curative intent (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated surgically with curative intent) No evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers
  • Pre-existing medical conditions precluding treatment (e.g. previous history of immune-related adverse reactions, pneumonitis, colitis, etc.)
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
  • History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
  • Active tuberculosis
  • Pregnancy or lactating mothers. Women of childbearing age must use contraception during treatment and for 5 months after the last dose of Atezolizumab. Acceptable methods are: oral contraceptives, hormonal implants, hormonal patches, IDU, Diaphragm with spermicides, cervical cape with spermicide, and condom with spermicide.
  • Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Received or will receive a live vaccine within 4 weeks prior to first dose of study drug. Influenza vaccination should be given during influenza season only (approximately October through May in the Northern Hemisphere and approximately April through September in the Southern Hemisphere). Patients must agree not to receive live, attenuated influenza vaccine (e.g., FluMist®) within 28 days prior to randomization, during treatment or within 5 months following the last dose of atezolizumab (for patients randomized to atezolizumab)
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Serum albumin < 2.5 g/dL
  • Active infection requiring IV systemic therapy
  • Receipt of therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
  • Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Prior allogeneic stem cell or solid organ transplant
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  • Patients with active Hepatitis B virus (HBV) or Hepatitis C virus (HCV)
  • Not willing or unable to sign a consent form

Contact:

  • Afsar Salimi, MSc
  • 5149341934 Ext. 71727

Location:

  • MUHC
  • Montreal Quebec H4A 3J1 Canada

View trial on ClinicalTrials.gov


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Neoadjuvant Immunotherapy With Durvalumab in Combination With Tremelimumab in Patients With Muscle-invasive Bladder Cancer Ineligible for Cisplatin-based Chemotherapy.


Condition: Muscle-invasive Bladder Cancer

Intervention:

  • Drug: Durvalumab (Imfinzi)
  • Drug: Tremelimumab

Purpose: The trial assess the safety and antitumor activity of the anti-PD-L1 antibody Durvalumab in combination with the anti-CTLA4 antibody Tremelimumab.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03234153

Sponsor: University Hospital Inselspital, Berne

Primary Outcome Measures:

  • Measure: Objective Response Rate
  • Time Frame: 16 weeks
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Adverse Events
  • Time Frame: 26 weeks
  • Safety Issue:
  • Measure: Recurrence-free Survival
  • Time Frame: 78 weeks
  • Safety Issue:
  • Measure: Overall Survival
  • Time Frame: 78 weeks
  • Safety Issue:

Estimated Enrollment: 68

Study Start Date: July 15, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Age ≥ 18 years
  • Signed Informed Consent Form
  • ECOG performance status of 0 or 1
  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder (T2-T4 and/or N+). Patients with mixed histologies are required to have a dominant transitional cell pattern.
  • Measurable disease according to RECIST v1.1 criteria
  • Representative fresh tumor specimen; TURB (transurethral resection of bladder ) specimens must contain a muscle invasive component (at least T2)
  • Ineligible to receive cisplatin-based neoadjuvant chemotherapy based on at least one of the following criteria:
  • Creatinin clearance less than 60ml/min (24h urine)
  • CTCAE Gr ≥ 2 hearing loss
  • CTCAE Gr ≥ 2 neuropathy
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
  • Body weight >30 kg
  • Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 14 days prior the first study treatment:
  • Absolute neutrophil count (ANC) ≥ 1500 cells/µl
  • WBC counts > 2500/µl
  • Platelet count ≥ 100,000/µl
  • Hemoglobin ≥ 9.0 g/dL
  • AST, ALT and alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN)
  • Serum bilirubin ≤ 1.5 x ULN
  • INR and aPTT ≤ 1.5 x ULN
  • Serum creatinine clearance (CrCl) ≥ 40 mL/min using the Cockcroft-Gault equation
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for premenopausal female. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.

Exclusion Criteria:

  • Known metastatic disease
  • Intravesical chemo- or biological/immune (BCG) therapy within 6 weeks of first treatment dose
  • Prio treatment with immune checkpoint blockade therapies like anti-CTLA-4, anti-PD1 and anti-PD-L1 therapeutic antibodies, including durvalumab and tremelimumab
  • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis or glomerulonephritis Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this study
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational drug.
  • Female patients who are pregnant or breast feeding as well as male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy.
  • Known allergy or hypersensitivity to any of the investigational study drugs or any of the study excipients.
  • Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
  • Uncontrolled intercurrent illness, including but limited to, ongoing infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina.
  • Patients with prior allogeneic stem cell or solid organ transplantation
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan
  • Positive test for HIV
  • Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen test at screening) or hepatitis C.
  • Active tuberculosis
  • Administration of a living, attenuated vaccine within 4 weeks prior to treatment start
  • Severe infection within 4 weeks prior to cycle 1, day 1
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior treatment start or anticipated requirement for systemic immunosuppressive medications during the trial. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids, and mineralocorticoids is allowed
  • Known allergy or hypersensitivity to any of the study drugs or any of the study excipients.

Contact:

  • Julian Schardt, MD
  • + 41 (0)31 632 81 95

Location:

  • Departement of Medical Oncology, University Hospital Berne
  • Berne 3010 Switzerland

View trial on ClinicalTrials.gov


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Transurethral En Bloc Versus Standard Resection of Bladder Tumour: A Multi-centre Randomised Controlled Trial (EB-StaR Study).


Condition: Bladder Cancer

Intervention:

  • Device: Bipolar transurethral standard resection
  • Device: Bipolar transurethral en bloc resection

Purpose: Conventionally, transurethral standard resection (SR) of bladder tumour is performed in a piecemeal manner. Transurethral en bloc resection (EBR) has been described as an alternate surgical technique in bladder tumour resection. By preventing tumour fragmentation and ascertaining complete tumour resection by histological assessment of the EBR specimen, we hypothesized that EBR could reduce disease recurrence as compared to SR.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02993211

Sponsor: Chinese University of Hong Kong

Primary Outcome Measures:

  • Measure: One-year recurrence rate
  • Time Frame: One year after the allocated treatment
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Detrusor muscle sampling rate
  • Time Frame: One week after the allocated treatment
  • Safety Issue:
  • Measure: Occurrence of obturator reflex
  • Time Frame: Intra-operative
  • Safety Issue:
  • Measure: Operative time
  • Time Frame: Immediately post-operative
  • Safety Issue:
  • Measure: Rate of mitomycin C instillation
  • Time Frame: One day after the allocated treatment
  • Safety Issue:
  • Measure: Hospital stay
  • Time Frame: Three days after the allocated treatment
  • Safety Issue:
  • Measure: 30-day complications
  • Time Frame: Thirty days after the allocated treatment
  • Safety Issue:
  • Measure: Residual disease upon second look transurethral resection surgery
  • Time Frame: Seven weeks after the allocated treatment
  • Safety Issue:
  • Measure: Upstaging of disease upon second look transurethral resection surgery
  • Time Frame: Seven weeks after the allocated treatment
  • Safety Issue:
  • Measure: One-year progression rate
  • Time Frame: One year after the allocated treatment
  • Safety Issue:

Estimated Enrollment: 350

Study Start Date: April 18, 2017

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Age ≥ 18 years old with informed consent

Exclusion Criteria:

  • Bladder tumour base with maximal dimension of >3cm (Anticipated difficulty in retrieving the specimen en bloc)
  • Bladder tumour detected during intravesical BCG therapy (BCG failure warrants more aggressive treatment, i.e. radical cystectomy)
  • Histological diagnosis other than NMIBC
  • Presence or prior history of upper urinary tract malignancy
  • ECOG performance status ≥ 3 (Confined to bed or chair more than 50% of waking hours)
  • ASA III or above (Patient with severe systemic disease)
  • History of bleeding disorder or use of anti-coagulants
  • Pregnancy
  • Presence of other active malignancy
  • Life expectancy of less than one year

Contact:

  • Jeremy YC Teoh, MBBS
  • +852 3505 2625

Locations:

  • Caritas Medical Centre
  • Hong Kong Hong Kong
  • Kwong Wah Hospital
  • Hong Kong Hong Kong
  • North District Hospital
  • Hong Kong Hong Kong
  • Our Lady of Maryknoll Hospital
  • Hong Kong Hong Kong
  • Pok Oi Hospital
  • Hong Kong Hong Kong
  • Prince of Wales Hospital
  • Hong Kong Hong Kong
  • Princess Margaret Hospital
  • Hong Kong Hong Kong
  • Queen Elizabeth Hospital
  • Hong Kong Hong Kong
  • Queen Mary Hospital
  • Hong Kong Hong Kong
  • Tseung Kwan O Hospital
  • Hong Kong Hong Kong
  • Tuen Mun Hospital
  • Hong Kong Hong Kong
  • Tung Wah Hospital
  • Hong Kong Hong Kong
  • United Christian Hospital
  • Hong Kong Hong Kong

View trial on ClinicalTrials.gov


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An International, Multicenter, Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab as First-line Treatment in Cisplatin-ineligible Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma


Condition: Urothelial Carcinoma

Intervention:

  • Drug: Rogaratinib (BAY1163877)
  • Drug: Atezolizumab
  • Drug: Placebo

Purpose: FORT-2 is designed to evaluate safety, efficacy, RP2D and PK of rogaratinib in combination with atezolizumab in patients with untreated FGFR-positive urothelial carcinoma. The study comprises two separate parts: Phase 1b (Part A) and Phase 2 (Part B).The study parts differ in design, objectives and treatment. The primary objectives of this Phase 1b study (Part A) are to determine the safety, tolerability,RP2D and pharmacokinetics of rogaratinib in combination with atezolizumab in these patients. The primary objective of the Part B is to compare progression-free survival (PFS) according to RECIST v1.1 of rogaratinib in combination with atezolizumab over placebo in combination with atezolizumab in untreated patients with FGFR-positive locally advanced or metastatic urothelial carcinoma. Of note, patients who participate in Part A are not allowed to participate in Part B. Part B will be initiated once the data from Part A supports continuation of the study, even if this occurs prior to primary completion of Part A. The sponsor may decide not to continue the study as a whole after completion of Part A if the data do not support further development.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03473756

Sponsor: Bayer

Primary Outcome Measures:

  • Measure: Number of subjects with Dose-limiting toxicities(DLTs) in Part A
  • Time Frame: Up to 21 days
  • Safety Issue:
  • Measure: Number of subjects with treatment-emergent adverse events (TEAEs) in Part A
  • Time Frame: Up to 5 months
  • Safety Issue:
  • Measure: Number of subjects with drug-related TEAEs in Part A
  • Time Frame: Up to 5 months
  • Safety Issue:
  • Measure: Number of subjects with treatment-emergent serious adverse events(TESAEs) in Part A
  • Time Frame: Up to 5 months
  • Safety Issue:
  • Measure: Progression Free Survival(PFS)
  • Time Frame: Up to 25 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Objective Response Rate(ORR) in Part A
  • Time Frame: Up to 5 months
  • Safety Issue:
  • Measure: Maximal plasma concentration (Cmax) of rogaratinib in Part A
  • Time Frame: At cycle 1 Day 1
  • Safety Issue:
  • Measure: Area under the curve(0-8) (AUC(0-8)) of rogaratinib in Part A
  • Time Frame: At cycle 1 Day 1
  • Safety Issue:
  • Measure: Disease Control Rate(DCR) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Duration of Response(DOR) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Overall Survival(OS) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Objective Response Rate (ORR) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Concentrations for rogaratinib in Part B
  • Time Frame: Cycle 1 Day 1(C1D1), C2D1, C3D1, C4D1, C5D1
  • Safety Issue:
  • Measure: Concentrations for atezolizumab in Part B
  • Time Frame: C1D1, C1D15
  • Safety Issue:
  • Measure: Number of subjects with treatment-emergent adverse events (TEAEs) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Number of subjects with drug-related TEAEs in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Number of subjects with treatment-emergent serious adverse events(TESAEs) in Part B
  • Time Frame: Up to 25 months
  • Safety Issue:
  • Measure: Number of subjects with significant change in vital signs, physical finding and clinical laboratory results
  • Time Frame: Up to 25 months
  • Safety Issue:

Estimated Enrollment: 210

Study Start Date: May 15, 2018

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Existence of archival or fresh tumor biopsy specimen for FGFR1/3 mRNA expression testing
  • High FGFR1 or 3 mRNA expression levels (RNAscope score of 3+ or 4+) in archival or fresh tumor biopsy specimen
  • Documented locally advanced (T4, any N; or any T, N2-3) or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria:
  • No prior systemic treatment for locally advanced or metastatic urothelial carcinoma. For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval > 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment-naïve in the metastatic setting. Prior local intra-vesical chemotherapy or prior local immunotherapy is allowed if completed at least 4 weeks before the first study drug administration. Regionally available standard of care options must be considered for all patients.
  • Ineligibility for cisplatin-based chemotherapy as defined by any one of the following criteria:
  • Impaired renal function (GFR > 30 but < 60 mL/min/1.73 m2) according to the modification of diet in renal disease (MDRD) abbreviated formula
  • A Hearing loss (measured by audiometry) of > 25 dB at two contiguous test frequencies in at least one ear.
  • Grade ≥ 2 peripheral neuropathy (i.e. sensory alteration or paresthesia including tingling)
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1. Exlusion criteria:
  • Active symptomatic or untreated brain metastases as determined by CT or MRI evaluation during screening and prior radiographic assessment.
  • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
  • History or current condition of an uncontrolled cardiovascular disease including any of the following conditions:
  • Congestive heart failure (CHF) NYHA Class 2 or greater, unstable angina (symptoms of angina at rest) or
  • New-onset angina (within last 3 months before the first study drug administration)
  • Myocardial infarction (MI) within past 6 months before the first study drug administration
  • Unstable cardiac arrhythmias requiring anti-arrhythmic therapy.
  • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or known left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
  • Current diagnosis of any retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion.
  • Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia).
  • Concomitant therapies that are known to increase serum calcium or phosphate levels (i.e. antacids, phosphate-containing laxatives oral/rectal, potassium phosphate) and that cannot be discontinued or switched to a different medication before the first study drug administration
  • Treatment with systemic corticosteroids or other systemic immunosuppressant medications within 2 weeks before the first study drug administration, or anticipated requirement for systemic immunosuppressive medications during the trial.

Contact:

  • Bayer Clinical Trials Contact
  • (+) 1-888-8422937

Locations:

  • University of Arizona Cancer Center
  • Tucson Arizona 85724 United States
  • University of California - Davis
  • Sacramento California 95817 United States
  • Comprehensive Cancer Center
  • Chicago Illinois 60637 United States
  • Barbara Ann Karmanos Cancer Institute
  • Detroit Michigan 48201 United States
  • Memorial Sloan-Kettering Cancer Center
  • New York New York 10065 United States
  • Krankenhaus der Elisabethinen Linz GmbH
  • Linz Oberösterreich 4020 Austria
  • Uniklinikum Salzburg - Landeskrankenhaus
  • Salzburg 5020 Austria
  • Krankenhaus der Barmherzigen Brüder
  • Wien 1020 Austria
  • Allgemeines Krankenhaus der Stadt Wien
  • Wien 1090 Austria
  • Institut Bergonié - Unicancer Nouvelle Aquitaine
  • Bordeaux Cedex 33076 France
  • Centre Oscar Lambret - Lille
  • Lille Cedex 59020 France
  • Centre René Gauducheau - Nantes
  • Nantes 44805 France
  • Eberhard-Karls-Universität Tübingen
  • Tübingen Baden-Württemberg 72076 Germany
  • Universitätsklinikum Essen
  • Essen Nordrhein-Westfalen 45122 Germany
  • Universitätsklinikum Köln
  • Köln Nordrhein-Westfalen 50937 Germany
  • Universitätsmedizin der Johannes Gutenberg Universität Mainz
  • Mainz Rheinland-Pfalz 55131 Germany
  • A.O.U. di Modena - Policlinico
  • Modena Emilia-Romagna 41124 Italy
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano Lombardia 20133 Italy
  • IRCCS Istituto Europeo di Oncologia (IEO)
  • Milano Lombardia 20141 Italy
  • IRCCS Istituto Oncologico Veneto (IOV)
  • Padova Veneto 35128 Italy
  • A.O.U. Integrata Verona
  • Verona Veneto 37134 Italy
  • National Cancer Center Hospital East
  • Kashiwa Chiba 277-8577 Japan
  • National Hospital Organization Shikoku Cancer Center
  • Matsuyama Ehime 791-0280 Japan
  • University of Tsukuba Hospital
  • Tsukuba Ibaraki 305-8576 Japan
  • The Cancer Institute Hospital of JFCR
  • Koto-ku Tokyo 135-8550 Japan
  • 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
  • Ciutat Sanitària i Universitaria de la Vall d'Hebron
  • Barcelona 08035 Spain
  • Hospital Clínic i Provincial de Barcelona
  • Barcelona 08036 Spain
  • Hospital de la Santa Creu i de Sant Pau
  • Barcelona 08041 Spain
  • Hospital Ramón y Cajal
  • Madrid 28034 Spain
  • Hospital General Universitario de Valencia
  • Valencia 46014 Spain

View trial on ClinicalTrials.gov


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A Randomized Phase II Study of Atezolizumab (MPDL3280A) Plus Recombinant Human IL-7 (CYT107) in Patients With Locally Advanced or Metastatic Urothelial Carcinoma


Condition: Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Recurrent Bladder Urothelial Carcinoma, Recurrent Renal Pelvis Urothelial Carcinoma, Recurrent Ureter Urothelial Carcinoma, Recurrent Urethral Urothelial Carcinoma, Stage III Bladder Cancer AJCC v8, Stage III Renal Pelvis Cancer AJCC v8, Stage III Ureter Cancer AJCC v8, Stage III Urethral Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8, Stage IV Renal Pelvis Cancer AJCC v8, Stage IV Ureter Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8

Intervention:

  • Drug: Atezolizumab
  • Biological: Glycosylated Recombinant Human Interleukin-7
  • Other: Laboratory Biomarker Analysis

Purpose: This phase II trial studies how well atezolizumab when given with glycosylated recombinant human interleukin-7 (CYT107) works in treating participants with urothelial carcinoma that has spread to nearby tissue or lymph nodes, cannot be removed by surgery, or has spread to other places in the body. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. CYT107 is a biological product naturally made by the body that may stimulate the immune system to destroy tumor cells. Giving atezolizumab and CYT107 may work better in treating participants with locally advanced, inoperable, or metastatic urothelial carcinoma.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03513952

Sponsor: National Cancer Institute (NCI)

Primary Outcome Measures:

  • Measure: Objective response rate (ORR)
  • Time Frame: Up to 2 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Clinical benefit rate (CBR) measured by RECIST version (v.) 1.1 and immune-related (ir) RECIST
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Progression-free survival (PFS)
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Duration of response (DOR)
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Overall survival
  • Time Frame: Up to 2 years
  • Safety Issue:

Estimated Enrollment: 54

Study Start Date: September 28, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Patients must have histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra
  • Note: mixed histology tumors allowed if predominant histology is urothelial carcinoma
  • Note: small cell or neuroendocrine carcinoma is not allowed if predominant
  • Patients either may be treatment-naive and considered ineligible for cisplatin-based chemotherapy or have recurrent disease after any prior platinum-based chemotherapy regimen and meet at least one of the following criteria:
  • Glomerular filtration rate ≥ 30 mL/min and < 60 mL/min (by Cockcroft-Gault)
  • Grade 2 or higher hearing loss
  • Grade 2 or higher peripheral neuropathy
  • Eastern Cooperative Oncology Group (ECOG) performance status 2
  • OR have recurrent disease after any prior platinum-based chemotherapy regimen
  • Patients must have measurable disease per RECIST 1.1 assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI)
  • ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
  • Patients must have a life expectancy of greater or equal to 12 weeks
  • Leukocytes ≥ 2,500/mcL
  • Absolute neutrophil count ≥ 1,000/mcL
  • Platelets ≥ 100,000/mcL
  • Hemoglobin ≥ 8 g/dL
  • Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (however, patients with known Gilbert's disease who have serum bilirubin level ≤ 3 × ULN may be enrolled)
  • Aspartate aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 × ULN (AST and/or ALT ≤ 5 × ULN for patients with liver involvement)
  • Alkaline phosphatase ≤ 2.5 × ULN (≤ 5 ± ULN for patients with documented liver involvement or bone metastases)
  • Creatinine clearance ≥ 30 mL/min/1.73 m^2 by Cockcroft-Gault
  • At the discretion of the treating physician, a 24-hour urine creatinine clearance could be obtained and utilized as the gold standard if creatinine clearance by Cockcroft-Gault is < 30, and prevents patient enrollment on the trial
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
  • Patients must provide tissue from an archival tumor sample (obtained within 2 years from screening visit) or newly obtained core, punch, or excisional biopsy of a tumor lesion if deemed relatively safe and technically feasible
  • Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours before receiving the first dose of study agent(s); if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Patients must have the ability to understand and the willingness to sign a written informed consent document
  • Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:
  • A stable regimen of highly active antiretroviral therapy (HAART)
  • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
  • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR) -based tests
  • Patients who have received more than 2 systemic cytotoxic chemotherapy regimens for metastatic urothelial carcinoma
  • Note: prior perioperative chemotherapy is allowed and is not counted as a line of therapy

Exclusion Criteria:

  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Patients who have had chemotherapy or radiotherapy within 2 weeks (4 weeks for nitrosoureas or systemic mitomycin C) before the initiation of study treatment
  • Patients who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1); however, the following therapies are allowed:
  • Hormone-replacement therapy or oral contraceptives
  • Herbal therapy ≥ 1 week before initiation of study treatment (herbal therapy intended as anticancer therapy must be discontinued at least 1 week before initiation of study treatment)
  • Palliative radiotherapy for bone metastases > 2 weeks before initiation of study treatment
  • Patients who have received prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody, or pathway -targeting agents
  • Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
  • Minimum of 12 weeks from the first dose of anti-CTLA-4 and >6 weeks from the last dose
  • No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
  • Patients who have received treatment with any other investigational agent within 4 weeks before initiation of study treatment
  • Patients who have received treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks before initiation of study treatment
  • Patients who have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti TNF] agents) within 2 weeks before initiation of study treatment
  • Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
  • The use of inhaled corticosteroids, and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
  • Patients taking bisphosphonate therapy for symptomatic hypercalcemia
  • Note: use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
  • Patients requiring treatment with a receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitor (e.g., denosumab) who cannot discontinue it before initiation of study treatment
  • Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
  • Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
  • Evaluable or measurable disease outside the CNS
  • No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
  • No history of intracranial hemorrhage or spinal cord hemorrhage
  • No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted
  • No neurosurgical resection or brain biopsy within 28 days before initiation of study treatment
  • Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
  • Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study
  • No stereotactic radiation or whole-brain radiation within 28 days before initiation of study treatment
  • Screening CNS radiographic study ≥ 4 weeks from completion of radiotherapy and ≥ 2 weeks from discontinuation of corticosteroids
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Patients who have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients with known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver/nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH); and inherited liver disease
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
  • Patient who have a history or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • Patients who have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Patients who have known additional malignancies other than UBC within 2 years before initiation of study treatment; exceptions include malignancies with a negligible risk of metastasis or death and treated with expected curative outcome (e.g., non-melanomatous skin cancers), or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer
  • Patients with active tuberculosis (TB)
  • Patients who have leptomeningeal disease
  • Patients who have severe infections within 4 weeks before initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia;
  • Exception: uncomplicated urinary tract infection will not be considered as a severe infection in these patients
  • Patients who have signs or symptoms of infection within 2 weeks before initiation of study treatment
  • Patients who have received oral or IV antibiotics within 2 weeks before initiation of study treatment; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
  • Patients who have major surgical procedure, other than for diagnosis, within 28 days before initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
  • Patients who have had a live, attenuated vaccine within 4 weeks before initiation of study treatment or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab.
  • Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 4 weeks before initiation of study treatment or at any time during the study
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina pectoris, cardiac arrhythmia, recent myocardial infarction (within the last 6 months), or psychiatric illness/social situations that would limit compliance with study requirements
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g., infectious) illness

Locations:

  • Kaiser Permanente-Riverside
  • Riverside California 92505 United States
  • University of Chicago Comprehensive Cancer Center
  • Chicago Illinois 60637 United States
  • East Jefferson General Hospital
  • Metairie Louisiana 70006 United States
  • Washington University School of Medicine
  • Saint Louis Missouri 63110 United States
  • Roswell Park Cancer Institute
  • Buffalo New York 14263 United States
  • Seattle Cancer Care Alliance
  • Seattle Washington 98109 United States

View trial on ClinicalTrials.gov


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An Open Label, Randomized, Phase III Trial, Evaluating Efficacy of Atezolizumab in Addition to One Year BCG (Bacillus CaLmette-Guerin) Bladder Instillation in BCG-naive Patients With High-risk Non-muscle Invasive Bladder cANcer


Condition: Bladder Cancer

Intervention:

  • Drug: BCG
  • Drug: Atezolizumab

Purpose: This is an open-label, randomized, multicentric study in patients with high-risk non-muscle invasive bladder cancer who had never received BCG for this disease. The objective is to evaluate the efficacy of atezolizumab as measured by recurrence-free survival.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03799835

Sponsor: UNICANCER

Primary Outcome Measures:

  • Measure: Recurrence free survival
  • Time Frame: 2 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression free survival
  • Time Frame: From randomization to the date of progression, assessed up to 5 years
  • Safety Issue:
  • Measure: Disease specific survival
  • Time Frame: From randomization to the date of death, assessed up to 5 years
  • Safety Issue:
  • Measure: Overall Survival
  • Time Frame: From randomization to the date of death, assessed up to 5 years
  • Safety Issue:
  • Measure: Disease worsening in each arm
  • Time Frame: From randomization to the date of death, assessed up to 5 years
  • Safety Issue:
  • Measure: Complete response in each arm
  • Time Frame: 6 weeks and 2 years after randomization
  • Safety Issue:
  • Measure: Complete response among patients with CIS
  • Time Frame: 6 weeks and 2 years after randomization
  • Safety Issue:
  • Measure: National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
  • Time Frame: Throughout study completion, assessed up to 5 years
  • Safety Issue:
  • Measure: Quality of life questionnaire (QLQ): QLQ-C30 questionnaire (EORTC)
  • Time Frame: At randomization, every 12 weeks for years 1 and 2 after randomization, then every 24 weeks for years 3 to 5 after randomization
  • Safety Issue:

Estimated Enrollment: 614

Study Start Date: January 17, 2019

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • 1. Signed informed consent form 2. Adult man and women ( age ≥18 years) 3. Any high risk non muscle invasive urothelial carcinoma histologically confirmed (mixed histology tumors allowed if urothelial carcinoma histology is predominant) defined on the TURBT as any of the Following :
  • T1 tumor and/or
  • High grade (G3) and/or
  • Carcinoma in situ (CIS) 4. Tumor tissue available from the surgery for central confirmation of the diagnosis and analysis the expression of PD-L1 5. At least one additional (second) resection of the primary tumor has been performed in case of T1 tumors, or incomplete initial TURB, or in case of doubt about completeness of a TURB, or if there is no muscle in the specimen (can be omitted if TaLG/G1 tumors or primary CIS only was found) without upstaging towards MIBC (EAU guidelines, 2017) 6. Absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis, abdomen, and chest no more than 42 days prior to the first study treatment 7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 8. Life expectancy ≥12 weeks 9. Systolic blood pressure (BP) <160 mmHg and diastolic BP <95 mmHg, as documented within 7 days prior to the first study treatment (hypertension allowed provided it is controlled) 10. Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 7 days prior to the first study treatment:
  • absolute neutrophil count (ANC) ≥1500 cells/μL
  • white blood cell (WBC) counts >2500/μL
  • Lymphocyte count ≥300/μL
  • Platelet count ≥100,000/μL
  • Hemoglobin ≥9.0 g/dL
  • aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and alkaline phosphatase ≤2.5 × the upper limit of normal (ULN)
  • Serum bilirubin ≤1.0 × ULN Patients with known Gilbert disease who have serum bilirubin level ≤3 × ULN may be enrolled.
  • Partial thromboplastin time (PTT)/Prothrombin Time (PT) ≤1.5 × ULN or international normalized ratio (INR) <1.7 × ULN
  • Calculated creatinine clearance ≥20 mL/min (Cockcroft-Gault formula) 11. 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 atezolizumab 12. Patients affiliated to the social security system 13. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

Exclusion Criteria:

  • 1. Patient having received previous BCG therapy for bladder cancer 2. Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment. Hormone-replacement therapy or oral contraceptives are authorized 3. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug, whichever is longer, prior to day 1 of study treatment 4. Malignancies other than urothelial cancer within 5 years prior to Day 1 of cycle 1 of treatment except the following:
  • Patients with localized low risk prostate cancer (defined as Stage ≤T2b, Gleason score ≤7, and PSA at prostate cancer diagnosis ≤20 ng/mL [if measured]) treated with curative intent and without prostate-specific antigen (PSA) recurrence are eligible.
  • Patients with low risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤7 and PSA ≤10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
  • Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of metastasis or death <5% at 5 years) are eligible provided they meet all of the following criteria: malignancy treated with expected curative intent (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) and no evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers. 5. Pregnancy or breastfeeding 6. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 7. Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation 8. History of autoimmune disease or history of immunosuppression, or conditions associated with congenital or acquired immune deficiency , including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 6 for a more comprehensive list of autoimmune diseases)
  • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
  • Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan may be eligible.
  • History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 9. Serum albumin <2.5 g/dL 10. Known HIV infection 11. Patients with known active hepatitis B virus (HBV; chronic or acute; defined as having a positive hepatitis B surface antigen (HBsAg) test at screening) or hepatitis C.
  • Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody (HBc Ab) and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to randomisation.
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 12. Known active tuberculosis 13. Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia 14. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1 15. Receipt of therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1 Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible. 16. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina.
  • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction <50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate. 17. Major surgical procedure other than for diagnosis within 4 weeks prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study 18. Prior allogeneic stem cell or solid organ transplant 19. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation if such a live, attenuated vaccine will be required during the study
  • Influenza vaccination should be given during influenza season only (approximately October through May in the Northern Hemisphere and approximately April through September in the Southern Hemisphere). Patients must agree not to receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1, at randomization, during treatment or within 5 months following the last dose of atezolizumab (for patients randomized to atezolizumab). 20. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications 21. Prior treatment with CD137 agonists or immune checkpoint−blockade therapies, including anti-CD40, anti−CTLA-4, anti−PD-1, and anti−PD-L1 therapeutic antibodies 22. Treatment with systemic immunostimulatory agents (including but not limited to interferons, interleukin 2 (IL-2)) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1 23. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
  • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea, multiple doses for contrast allergy) may be enrolled in the study.
  • The use of inhaled or low-dose (e.g., ≤10 mg/day prednisone) corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, mineralocorticoids (e.g., fludrocortisone for adrenal insufficiency) and low-dose corticosteroids for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. 24. Person deprived of their liberty or under protective custody or guardianship

Contact:

  • Soazig Nénan-Le Ficher
  • +33185343113

Locations:

  • Hôpital G. Montpied
  • Clermont-Ferrand 63003 France
  • Clinique Claude Bernard
  • Ermont 95120 France
  • CHU Grenoble
  • Grenoble 38043 France
  • Hôpital privé Toulon - Sainte Marguerite
  • Hyères 83400 France
  • Hôpital privé de la Louvière
  • Lille 59800 France
  • Insitut Paoli Calmette
  • Marseille 13009 France
  • Hôpital européen Georges Pompidou
  • Paris 75010 France
  • Hôpital Saint Louis
  • Paris 75010 France
  • Institut Mutualiste Montsouris
  • Paris 75014 France
  • Hôpital Diaconesses- Croix Saint Simon
  • Paris 75020 France
  • Hôpital La Pitié Salpétrière
  • Paris 75651 France
  • Hôpitaux d'instruction des armées Begin
  • Saint-Mandé 94160 France
  • Hôpital Foch
  • Suresnes 92150 France
  • Hôpitaux Leman
  • Thonon-les-Bains 74200 France

View trial on ClinicalTrials.gov


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A Phase III Randomized, Open-Label, Multi-Center, Global Study of Durvalumab and Bacillus Calmette-Guerin (BCG) Administered as Combination Therapy Versus BCG Alone in High-Risk, BCG Naïve Non-Muscle Invasive Bladder Cancer Patients


Condition: Non-muscle-invasive Bladder Cancer

Intervention:

  • Biological: Durvalumab (MEDI4736)
  • Biological: Bacillus Calmette-Guerin (BCG)

Purpose: This is a randomized, open-label, multi-center, global, phase III study to determine the efficacy and safety of Durvalumab + BCG combination therapy in the treatment of patients with non-muscle-invasive bladder cancer.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03528694

Sponsor: AstraZeneca

Primary Outcome Measures:

  • Measure: The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of Disease free survival (DFS) in patients with NMIBC
  • Time Frame: Up to 4 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of DFS after 24 months of last subject's last dose of IP
  • Time Frame: Up to 4 years
  • Safety Issue:
  • Measure: Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the EORTC QLQ-C30 questionnaire
  • Time Frame: Up to 4 years
  • Safety Issue:
  • Measure: Patient-reported treatment tolerability using specific PRO CTCAE symptoms
  • Time Frame: Up to 4 years
  • Safety Issue:
  • Measure: The serum concentration of Durvalumab plus BCG combination therapies
  • Time Frame: Up to 4 years
  • Safety Issue:
  • Measure: The immunogenicity of Durvalumab when used in combination with BCG treatment assessed by descriptive summary of presence of ADAs
  • Time Frame: Up to 4 years
  • Safety Issue:
  • Measure: The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of OS
  • Time Frame: Up to 7 years
  • Safety Issue:
  • Measure: The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic disease
  • Time Frame: Up to 7 years
  • Safety Issue:
  • Measure: The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of DFS after 24 months of last subject's last dose of IP
  • Time Frame: Up to 4 years
  • Safety Issue:
  • Measure: The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of DFS after 24 months of last subject's last dose of IP
  • Time Frame: Up to 4 years
  • Safety Issue:
  • Measure: The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of OS
  • Time Frame: Up to 7 years
  • Safety Issue:
  • Measure: The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of OS
  • Time Frame: Up to 7 years
  • Safety Issue:
  • Measure: The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic disease
  • Time Frame: Up to 7 years
  • Safety Issue:
  • Measure: The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of time to muscle invasive bladder cancer and/or metastatic disease
  • Time Frame: Up to 7 years
  • Safety Issue:
  • Measure: Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the the EORTC QLQ NMIBC24 questionnaire
  • Time Frame: Up to 4 years
  • Safety Issue:

Estimated Enrollment: 975

Study Start Date: May 14, 2018

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum 130 Years
  • Gender: All

Inclusion Criteria:

  • For inclusion in the study, patients should fulfill the following criteria:
  • Aged at least 18 years
  • BCG-naïve (patients who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry are eligible)
  • Local histological confirmation (based on pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high risk tumor is defined as one of the following
  • T1 tumor
  • High grade/ G3 tumor
  • CIS
  • Multiple and recurrent and large (with diameter of largest tumor ≥3 cm) tumors (all conditions must be met in this point)
  • Complete resection of all Ta/T1 papillary disease prior to randomization, with the TURBT removing high-risk NMIBC performed not more than 4 months before randomization in the study. Patients with residual CIS after TURBT are eligible
  • No prior radiotherapy for bladder cancer
  • No prior exposure to immune-mediated therapy of cancer including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 antibodies. Patients who have been treated with anticancer vaccines will be excluded Exclusion Criteria: Patients should not enter the study if any of the following

Exclusion Criteria:

  • Patients should not enter the study if any of the following exclusion criteria are fulfilled:
  • Evidence of muscle-invasive, locally advanced, metastatic, and/or extra vesical bladder cancer (ie, T2, T3, T4, and / or stage IV)
  • Concurrent extravesical (ie, urethra, ureter, or renal pelvis), non-muscle-invasive transitional cell carcinoma of the urothelium
  • Previous investigational product (IP) assignment in the present study
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer related conditions (eg, hormone replacement therapy) is acceptable. Chemotherapy for previous instances of NMIBC is acceptable.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
  • Patients with celiac disease controlled by diet alone
  • History of another primary malignancy except for
  • Malignancy treated with curative intent and with no known active disease ≥ 2 years before the first dose of IP and of low potential risk for recurrence during the study period
  • Adequately treated nonmelanoma skin cancer or lentigo maligna withoutevidence of disease
  • Adequately treated CIS without evidence of disease
  • Prostate cancer (tumor/node/metastasis stage) of stage ≤ T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication)

Contact:

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

Locations:

  • Research Site
  • Auchenflower 4066 Australia
  • Research Site
  • Box Hill 3128 Australia
  • Research Site
  • Brisbane 4122 Australia
  • Research Site
  • Kogarah 2217 Australia
  • Research Site
  • Orange 2800 Australia
  • Research Site
  • Parkville 3000 Australia
  • Research Site
  • Westmead 2145 Australia
  • Research Site
  • Wollongong 2500 Australia
  • Research Site
  • Innsbruck 6020 Austria
  • Research Site
  • Linz 4020 Austria
  • Research Site
  • Wien 1090 Austria
  • Research Site
  • Brussels 1070 Belgium
  • Research Site
  • Gent 9000 Belgium
  • Research Site
  • Leuven 3000 Belgium
  • Research Site
  • Roeselare 8800 Belgium
  • Research Site
  • Burnaby British Columbia V5G 2X6 Canada
  • Research Site
  • Vancouver British Columbia V5Z 1M9 Canada
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  • Halifax Nova Scotia B3H 2Y9 Canada
  • Research Site
  • Hamilton Ontario L8V 5C2 Canada
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  • Kingston Ontario K7L 3J7 Canada
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  • Ottawa Ontario K1H 8L6 Canada
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  • Toronto Ontario M4N 3M5 Canada
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  • Toronto Ontario M5G 2M9 Canada
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  • Chicoutimi Quebec G7H 5H6 Canada
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  • Montreal Quebec H2X 3E4 Canada
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  • Quebec G1R 3S1 Canada
  • Research Site
  • Amiens Cedex 1 80054 France
  • Research Site
  • Angers Cedex 01 49033 France
  • Research Site
  • Bordeaux Cedex 33076 France
  • Research Site
  • LYON cedex 03 69437 France
  • Research Site
  • Marseille 13003 France
  • Research Site
  • Montpellier CEDEX 5 34295 France
  • Research Site
  • Strasbourg Cedex 67091 France
  • Research Site
  • Suresnes 92151 France
  • Research Site
  • Berlin 12200 Germany
  • Research Site
  • Duisburg 47179 Germany
  • Research Site
  • Hamburg 22399 Germany
  • Research Site
  • Hannover 30625 Germany
  • Research Site
  • Heidelberg 69120 Germany
  • Research Site
  • Heinsberg 52525 Germany
  • Research Site
  • Köln 50968 Germany
  • Research Site
  • Marburg 35043 Germany
  • Research Site
  • Mettmann 40822 Germany
  • Research Site
  • Mühlheim An Der Ruhr 45468 Germany
  • Research Site
  • München 81377 Germany
  • Research Site
  • Münster 48149 Germany
  • Research Site
  • Nürtingen 72766 Germany
  • Research Site
  • Wesel Germany
  • Research Site
  • Würselen 52146 Germany
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  • Zirndorf 90513 Germany
  • Research Site
  • Bunkyo-ku 113-8603 Japan
  • Research Site
  • Fukuoka 812-8582 Japan
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  • Kanazawa-shi 920-8641 Japan
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  • Kita-gun 761-0793 Japan
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  • Koto-ku 135-8550 Japan
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  • Matsuyama-shi 791-0280 Japan
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  • Miyazaki-city 889-1692 Japan
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  • Nagasaki-shi 852-8501 Japan
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  • Nagoya-shi 467-0001 Japan
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  • Okayama-shi 700-8558 Japan
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  • Osaka-shi 541-8567 Japan
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  • Osakasayama-shi 589-8511 Japan
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  • Sapporo-shi 060-8543 Japan
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  • Shinjuku-ku 160-8582 Japan
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  • Toyama-shi 930-0194 Japan
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  • Tsukuba-shi 305-8576 Japan
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  • Yokohama-shi 232-0024 Japan
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  • Arnhem 6815 AD Netherlands
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  • Brussels 1090 Netherlands
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  • Leiden 2333 ZA Netherlands
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  • Leuven 3000 Netherlands
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  • Białystok 15-950 Poland
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  • Bydgoszcz 85-681 Poland
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  • Gdańsk 80-952 Poland
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  • Koszalin 75-581 Poland
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  • Olsztyn 10-513 Poland
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  • Piotrków Trybunalski 97-300 Poland
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  • Poznań 60-848 Poland
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  • Warszawa 02-005 Poland
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  • Warszawa 02-781 Poland
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  • Wroclaw 53-413 Poland
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  • Wrocław 50-556 Poland
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  • Ivanovo 153040 Russian Federation
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  • Krasnoyarsk 660133 Russian Federation
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  • Moscow 115280 Russian Federation
  • Research Site
  • Nizhniy Novgorod 603074 Russian Federation
  • Research Site
  • Obninsk 249036 Russian Federation
  • Research Site
  • Omsk 644013 Russian Federation
  • Research Site
  • Saint Petersburg 195271 Russian Federation
  • Research Site
  • St Petersburg 194044 Russian Federation
  • Research Site
  • St. Petersburg 194017 Russian Federation
  • Research Site
  • St. Petersburg 197758 Russian Federation
  • Research Site
  • St.Petersburg 191014 Russian Federation
  • Research Site
  • Vladimir 600020 Russian Federation
  • Research Site
  • Vologda 160012 Russian Federation
  • Research Site
  • Yaroslavl 150054 Russian Federation
  • Research Site
  • Banka 921 01 Slovakia
  • Research Site
  • Bratislava 811 08 Slovakia
  • Research Site
  • Bratislava 812 50 Slovakia
  • Research Site
  • Martin 036 59 Slovakia
  • Research Site
  • Presov 08001 Slovakia
  • Research Site
  • Badajoz 06008 Spain
  • Research Site
  • Barcelona 08035 Spain
  • Research Site
  • Barcelona 08036 Spain
  • Research Site
  • Barcelona 08208 Spain
  • Research Site
  • Elche(Alicante) 03202 Spain
  • Research Site
  • Madrid 28040 Spain
  • Research Site
  • Madrid 28041 Spain
  • Research Site
  • Madrid 28046 Spain
  • Research Site
  • Malaga 29010 Spain
  • Research Site
  • Oviedo 33011 Spain
  • Research Site
  • Pamplona 31008 Spain
  • Research Site
  • Pozuelo de Alarcon 28223 Spain
  • Research Site
  • Sevilla 41009 Spain
  • Research Site
  • Sevilla 41014 Spain
  • Research Site
  • Valencia 46014 Spain
  • Research Site
  • Birmingham B15 2TH United Kingdom
  • Research Site
  • Cleveland TS4 3BW United Kingdom
  • Research Site
  • Glasgow G12 0YN United Kingdom
  • Research Site
  • Guildford CU2 7XX United Kingdom
  • Research Site
  • London EC1A 7BE United Kingdom
  • Research Site
  • London NW1 2PG United Kingdom
  • Research Site
  • London SE1 9RY United Kingdom
  • Research Site
  • Sheffield S10 2RX United Kingdom
  • Research Site
  • Southampton SO16 6YD United Kingdom
  • Research Site
  • Taunton TA1 5DA United Kingdom

View trial on ClinicalTrials.gov


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A Phase 1 Study of Cabozantinib Plus Nivolumab (CaboNivo) Alone or in Combination With Ipilimumab (CaboNivoIpi) in Patients With Advanced/Metastatic Urothelial Carcinoma and Other Genitourinary Tumors


Condition: Advanced Clear Cell Renal Cell Carcinoma, Infiltrating Bladder Urothelial Carcinoma Sarcomatoid Variant, Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant, Kidney Small Cell Carcinoma, Metastatic Bladder Small Cell Carcinoma, Metastatic Bladder Squamous Cell Carcinoma, Metastatic Bladder Urothelial Carcinoma, Metastatic Kidney Medullary Carcinoma, Metastatic Malignant Genitourinary System Neoplasm, Metastatic Malignant Neoplasm in the Bone, Metastatic Penile Carcinoma, Metastatic Renal Cell Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Sarcomatoid Renal Cell Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Progressive Disease, Squamous Cell Carcinoma of the Penis, Stage III Bladder Adenocarcinoma AJCC v6 and v7, Stage III Bladder Squamous Cell Carcinoma AJCC v6 and v7, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Penile Cancer AJCC v7, Stage III Renal Cell Cancer AJCC v7, Stage III Renal Pelvis Cancer AJCC v7, Stage III Ureter Cancer AJCC v7, Stage III Urethral Cancer AJCC v7, Stage IIIa Penile Cancer AJCC v7, Stage IIIb Penile Cancer AJCC v7, Stage IV Bladder Adenocarcinoma AJCC v7, Stage IV Bladder Squamous Cell Carcinoma AJCC v7, Stage IV Bladder Urothelial Carcinoma AJCC v7, Stage IV Penile Cancer AJCC v7, Stage IV Renal Cell Cancer AJCC v7, Stage IV Renal Pelvis Cancer AJCC v7, Stage IV Ureter Cancer AJCC v7, Stage IV Urethral Cancer AJCC v7

Intervention:

  • Drug: Cabozantinib
  • Drug: Cabozantinib S-malate
  • Biological: Ipilimumab
  • Biological: Nivolumab

Purpose: This phase I trial studies the side effects and best doses of cabozantinib s-malate and nivolumab with or without ipilimumab in treating patients with genitourinary (genital and urinary organ) tumors that have spread to other places in the body (metastatic). Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving cabozantinib s-malate and nivolumab alone or with ipilimumab works better in treating patients with genitourinary tumors.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02496208

Sponsor: National Cancer Institute (NCI)

Primary Outcome Measures:

  • Measure: Recommended phase II dose (Phase I)
  • Time Frame: Up to 4-6 weeks
  • Safety Issue:
  • Measure: Incidence of adverse events (Phase I)
  • Time Frame: Up to 3 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Clinical response rate
  • Time Frame: Up to 3 years
  • Safety Issue:
  • Measure: Fraction of patients who have been identified as being alive and progression free at two months
  • Time Frame: At 2 months
  • Safety Issue:
  • Measure: PDL-1 and MET expression
  • Time Frame: Up to day 1 of final cycle
  • Safety Issue:

Estimated Enrollment: 152

Study Start Date: July 9, 2015

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Patients in the phase I portion must have:
  • Histologically confirmed diagnosis of metastatic, genitourinary solid tumor
  • Metastatic disease defined as new or progressive lesions on cross-sectional imaging; patients must have at least:
  • One evaluable site of disease
  • Or, appearance of one new bone lesion
  • Patients in the expansion portion must have:
  • Histologically confirmed diagnosis of metastatic:
  • Urothelial carcinoma of the bladder, urethra, ureter, renal pelvis, OR
  • Clear cell renal cell carcinoma OR
  • Adenocarcinoma of the bladder OR
  • Non-resectable squamous cell carcinoma of the penis OR
  • Squamous or small cell carcinoma of the bladder, renal medullary carcinoma (RMC), sarcomatoid bladder and renal cell carcinomas, plasmacytoid carcinoma of the bladder or other rare bladder/kidney cancer histology AND
  • Patients with urothelial cancer or renal cell carcinoma must have progressive metastatic disease defined as new or progressive lesions on cross-sectional imaging; patients must have at least:
  • One measurable site of disease (according to RECIST criteria) or bone disease by NaF PET/CT
  • Patients must have either progressed on least one standard therapy or there must be no standard treatment that has been shown to prolong survival for the patient's disease (patients with urothelial carcinoma who are cisplatin-ineligible may receive protocol therapy as a first line therapy); patients may have received any number of prior cytotoxic agents
  • Karnofsky performance status >= 70%
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,200/mcL
  • Platelets >= 75,000/mcL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN); for subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =< 3.0 mg/dL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional upper limit of normal (ULN)
  • Creatinine =< 1.5 x ULN OR creatinine clearance >= 40 mL/min/1.73 m^2 (calculated using the Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
  • Hemoglobin >= 9 g/dL
  • Serum albumin >= 2.8 g/dL
  • Lipase and amylase =< 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
  • Urine protein/creatinine ratio (UPCR) =< 2
  • Serum phosphorus >= lower limit of normal (LLN) (if below LLN, for asymptomatic patients replacement may be initiated if clinically indicated without delaying the start of study treatment)
  • Serum calcium >= LLN (if below LLN, for asymptomatic patients replacement may be initiated if clinically indicated without delaying the start of study treatment)
  • Serum magnesium >= LLN (if below LLN, for asymptomatic patients replacement may be initiated if clinically indicated without delaying the start of study treatment)
  • Serum potassium >= LLN (if below LLN, for asymptomatic patients replacement may be initiated if clinically indicated without delaying the start of study treatment)
  • Women of childbearing potential must have a negative pregnancy test at screening; women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal; postmenopause is defined as amenorrhea >= 12 consecutive months; Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
  • The effects of the drugs used in this trial on the developing human fetus are unknown; however, cabozantinib was embryolethal in rats at exposures below the 140mg dose in the label, with increased incidences of skeletal variations in rats and visceral variations and malformations in rabbits; for this reason and because tyrosine kinase inhibitors agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception, as defined below, prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of all study medications; women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 5 months after completion of all study medications
  • Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 5 or 7 months for women or men respectively, after the last dose of study drugs, even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 5 or 7 months for women and men respectively after the last dose of study drugs
  • Tissue availability for programmed cell death ligand 1 (PD-L1) expression is mandatory for enrollment; however if archived tissue is unavailable the patient will be given the option to consent to pre and post treatment tissue biopsies; tissue biopsies will be collected pretreatment (prior to the first dose of therapy) and post treatment (after at least 1 dose, preferably 2 doses of nivolumab)
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment
  • Patients who have been previously treated with MET or vascular endothelial growth factor receptor (VEGFR) inhibitors (except for patients on renal cell cancer [RCC] cohort) are not eligible for the expansion cohorts but can enroll in the phase I portion
  • Prior treatment with any therapy on the programmed cell death 1 (PD-1)/PD-L1 axis or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors unless enrolling the urothelial carcinoma with previous checkpoint inhibition therapy expansion cohort
  • The subject has received radiation therapy:
  • To the thoracic cavity or abdomen within 3 months before the first dose of study treatment, or has ongoing complications, or is without complete recovery and healing from prior radiation therapy
  • To bone or brain metastasis within 3 weeks before the first dose of study treatment
  • To any other site(s) within 28 days before the first dose of study treatment
  • The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
  • The subject has received prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
  • The subject has received prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment; subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate
  • The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
  • The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae
  • The subject has active brain metastases or epidural disease; subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible; neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment; baseline brain imaging with contrast-enhanced CT or magnetic resonance imaging (MRI) scans for subjects with known brain metastases is required to confirm eligibility
  • The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test >= 1.5 x the laboratory ULN within 7 days before the first dose of study treatment
  • The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, thrombin or factor Xa inhibitors; aspirin (up to 325 mg/day), low-dose warfarin (=< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
  • The subject requires chronic concomitant treatment of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort); Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • The subject has experienced any of the following:
  • Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
  • Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment
  • Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
  • The subject has tumor invading any major blood vessels
  • The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders including:
  • Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening
  • Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
  • The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard
  • Any history of congenital long QT syndrome
  • Any of the following within 6 months before the first dose of study treatment:
  • Unstable angina pectoris
  • Clinically-significant cardiac arrhythmias
  • Stroke (including transient ischemic attack [TIA], or other ischemic event)
  • Myocardial infarction
  • Cardiomyopathy
  • Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
  • Any of the following that have not resolved within 28 days before the first dose of study treatment
  • Intra-abdominal tumor/metastases invading GI mucosa
  • Active peptic ulcer disease
  • Diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
  • Malabsorption syndrome
  • Any of the following within 6 months before the first dose of study treatment:
  • Abdominal fistula
  • Gastrointestinal perforation
  • Bowel obstruction or gastric outlet obstruction
  • Intra-abdominal abscess; Note: complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months before the first dose of study treatment
  • Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
  • Other clinically significant disorders such as:
  • Severe active infection requiring systemic treatment within 14 days before the first dose of study treatment
  • Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
  • History of organ transplant
  • Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid stimulating hormone [TSH], thyroid replacement may be initiated if clinically indicated without delaying the start of study treatment)
  • History of major surgery as follows:
  • Major surgery within 3 months of the first dose of cabozantinib; however, if there were no wound healing complications, patients with rapidly growing aggressive cancers, may start as soon as 6 weeks if wound has completely healed post-surgery
  • Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications excluding core biopsies and Mediport placement
  • In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery
  • The subject is unable to swallow tablets
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
  • For disease specific studies: the subject has had evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment
  • Hist

Locations:

  • 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
  • University of California Davis Comprehensive Cancer Center
  • Sacramento California 95817 United States
  • National Institutes of Health Clinical Center
  • Bethesda Maryland 20892 United States
  • NCI - Center for Cancer Research
  • Bethesda Maryland 20892 United States
  • Rutgers Cancer Institute of New Jersey
  • New Brunswick New Jersey 08903 United States
  • Ohio State University Comprehensive Cancer Center
  • Columbus Ohio 43210 United States

View trial on ClinicalTrials.gov


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Gemcitabine-cisplatin Plus Avelumab or Gemcitabine-cisplatin as First-line Treatment of Patients With Locally Advanced or Metastatic Urothelial Bladder Carcinoma (GCISAVE)


Condition: Bladder Carcinoma

Intervention:

  • Drug: Avelumab
  • Drug: GC

Purpose: This study will assess efficacy (based on response rate) and safety (based on grade ≥ 3 severe adverse effects) of the combination Gemcitabine Cisplatin (GC) + anti-PD-L1 (avelumab) in first-line treatment for locally advanced or metastatic urothelial bladder cancer patients, after 6 cycles of treatment (or at 18 weeks if less than 6 cycles have been given, or earlier if a second line treatment is needed, before this new anticancer treatment has been started).

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03324282

Sponsor: University Hospital, Bordeaux

Primary Outcome Measures:

  • Measure: Efficacy: objective response rate with RECIST 1.1 with GC + avelumab
  • Time Frame: At the end of cycle 6 (each cycle is 21 days)
  • Safety Issue:
  • Measure: Safety: proportion of severe toxicity with GC + avelumab
  • Time Frame: At the end of cycle 6 (each cycle is 21 days)
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Immunological capacities in peripheral blood of GC alone and GC+avelumab groups
  • Time Frame: During treatment and after the 6 cycles of treatment (EOT + 3, 6, 9 and 12 months
  • Safety Issue:
  • Measure: Specific immunological toxicity documented and recorded using NCI CTCAE version 4.0
  • Time Frame: At the end of cycle 6 (each cycle is 21 days)
  • Safety Issue:
  • Measure: Duration of response
  • Time Frame: Up to 18 months
  • Safety Issue:
  • Measure: Progression-free survival
  • Time Frame: At 18 months in GC+avelumab treated patients
  • Safety Issue:
  • Measure: Overall survival
  • Time Frame: At 18 months in GC+avelumab treated patients
  • Safety Issue:
  • Measure: GC+avelumab efficacy according to the expression of PD-L1 at the tumor site
  • Time Frame: At the end of cycle 6 (each cycle is 21 days)
  • Safety Issue:
  • Measure: GC+avelumab efficacy according to the immune infiltrate populations at the tumor level and/or the tumor surroundings
  • Time Frame: At the end of cycle 6 (each cycle is 21 days)
  • Safety Issue:

Estimated Enrollment: 90

Study Start Date: February 2, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Signed and dated informed consent;
  2. Male or female, age ≥18 years at time of informed consent signature;
  3. Histological confirmed locally advanced (any T N2-3) or metastatic urothelial bladder carcinoma, eligible to first-line treatment (previous neo adjuvant or adjuvant treatment must have been given and stopped more than one year before);
  4. Evidence of progressive disease in the previous 6 months, documented by chest and/or abdominal CT-scan or MRI;
  5. Measurable disease according to RECIST 1.1;
  6. Karnofsky index ≥ 70%;
  7. Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour specimen (infiltrative urothelial bladder carcinoma or metastasis) collected within 12 months before Cycle 1 Day 1;
  8. At least 3 weeks since the end of prior local intravesical treatment (BCG-therapy or ametycine) with resolution of all treatment-related toxicity to grade ≤1 (NCI CTCAE 4.0);
  9. Palliative local treatment is allowed if performed ≥ 2 weeks prior study entry for radiotherapy, cimentoplasty or minor surgery, and ≥4 weeks for major surgery;
  10. Adequate organ function as defined by the following criteria:
  11. Absolute White Blood Cells count (WBC) ≥ 2000 cells/mm3
  12. Absolute Neutrophils count (ANC) ≥ 1500 cells/mm3
  13. Platelets ≥100 000 cells/mm3
  14. Hemoglobin ≥ 9.0 g/dL
  15. Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
  16. Calculated creatinine clearance ≥ 60 mL/min
  17. Women of childbearing potential must have a negative serum βHCG or urine pregnancy test within 7 days prior to initiation of treatment; both sexually active females and males (and their female partners) patients must agree to use two methods of effective contraception one of them being a barrier method, or to abstain from sexual activity during the study, for at least 3 months after the last administration of study treatment;
  18. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures;
  19. Patient affiliated to a social security system or beneficiary of the same.

Exclusion Criteria:

  1. Other prior first-line therapy;
  2. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment; focal radiation therapy less than 14 days prior to the first day of the first cycle;
  3. Other invasive malignancy within 3 years (except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast); Patient with low risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 7 and PSA ≤ 10ng/mL) who are treatment-naïve and undergoing active surveillance are eligible;
  4. 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;
  5. Symptomatic central nervous system (CNS) metastases or untreated CNS metastases requiring concurrent treatment;
  6. 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;
  7. Uncontrolled adrenal insufficiency;
  8. Active chronic liver disease;
  9. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, 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;
  10. Active infection requiring systemic antibiotic;
  11. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines;
  12. 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);
  13. Major surgery less than 28 days prior to the first day of the first cycle. Minor surgery less than 14 days prior to the first day of the first cycle;
  14. 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;
  15. History of primary immunodeficiency;
  16. History of organ transplant including allogeneic stem-cell transplantation;
  17. 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);
  18. Women who are pregnant or lactating;
  19. Known history of testing positive for HIV or known acquired immunodeficiency syndrome;
  20. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection.

Contact:

  • Alain RAVAUD, MD. PhD
  • +33 (0)5 56 79 58 08

Locations:

  • CHU de Besançon
  • Besançon France
  • CHU de Bordeaux
  • Bordeaux France
  • Institut Bergonié
  • Bordeaux France
  • Centre François Baclesse
  • Caen France
  • Centre Léon Bérard
  • Lyon France
  • Institut Paoli Calmettes
  • Marseille France
  • Institut de cancérologie de l'Ouest - René Gauducheau
  • Nantes France
  • Hôpital Européen Georges-Pompidou, AP-HP
  • Paris France
  • Hôpital Saint-Louis, AP-HP
  • Paris France
  • CHU de Poitiers
  • Poitiers France
  • CHU de Strasbourg
  • Strasbourg France
  • Institut Universitaire du Cancer de Toulouse - Oncopole
  • Toulouse France
  • Institut Gustave Roussy
  • Villejuif France

View trial on ClinicalTrials.gov


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Study of the Efficacy of Maintenance Therapy by UFT or BCG for Superficial Bladder Cancer Against Recurrence in Urological Oncology Council of Northern Tokyo: EMBARK Study


Condition: Bladder Cancer

Intervention:

  • Drug: Bacille Calmette-Guerin
  • Drug: uracil-tegafur

Purpose: The purpose of this prospective randomized controlled study is to prove the non-inferiority of UFT maintenance therapy to BCG maintenance therapy for preventing recurrences of superficial bladder cancer.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01082510

Sponsor: Urological Oncology Council of Northern Tokyo

Primary Outcome Measures:

  • Measure: Relapse-free survival rate
  • Time Frame: Three-year
  • Safety Issue:

Estimated Enrollment: 288

Study Start Date: January 2010

Phase: Phase 3

Eligibility:

  • Age: minimum 20 Years maximum 80 Years
  • Gender: All

Inclusion Criteria:

  • Superficial bladder cancer
  • Completion of transurethral resection of bladder tumor (TUR-Bt)
  • Completion of BCG induction therapy after TUR-Bt. In principle, BCG induction therapy consists of the successive weekly intravesical administration of 81 mg of BCG-Connaught strain or 80 mg of BCG-Japan strain for 6 weeks after the completion of TUR-Bt.
  • Age 20 to 80 years
  • ECOG performance status of 0 or 1
  • Bladder capacity ≥ 150 mL
  • Capable of oral UFT administration
  • Expected life prognosis ≥ 3 years
  • Hematopoietic WBC ≥ 3,000/mm^3
  • Neutrophil ≥ 1,500/mm^3
  • Platelet ≥ 100,000/mm^3
  • Hepatic AST and ALT ≤ 2 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 mg/dL
  • Hemoglobin ≤ 9.0 g/dL
  • Creatinine ≤ 1.5 mg/dL

Exclusion Criteria:

  • Bladder cancer located in prostatic part of the urethra
  • Anamnesis of bladder cancer classified as cT2, cT3 or cT4
  • Anamnesis of metastatic bladder cancer
  • Anamnesis of upper urinary tract carcinoma in situ
  • Anamnestic treatment of intravesical BCG administration within previous 6 months
  • Prior anticancer chemotherapy or radiotherapy
  • Severe complication
  • Presence of contraindications for the administration of BCG or UFT
  • Pregnancy, lactation

Contact:

  • Satoru Muto, PhD
  • +81 3 3964 2497

Location:

  • Department of Urology, Teikyo University Hospital
  • Itabashi-ku Tokyo Japan

View trial on ClinicalTrials.gov


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Afatinib Dimaleate in Treating Patients With Advanced Refractory Urothelial Cancer


Condition: Distal Urethral Cancer, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Urethral Cancer, Stage III Bladder Cancer, Stage III Urethral Cancer, Stage IV Bladder Cancer, Stage IV Urethral Cancer, Ureter Cancer

Intervention:

  • Drug: afatinib dimaleate
  • Other: laboratory biomarker analysis

Purpose: This phase II trial studies how well afatinib dimaleate works in treating patients with urothelial cancer that cannot be removed surgically and has grown after treatment with standard first-line chemotherapy. Afatinib dimaleate may turn off the function of the epidermal growth factor (EGF) and human epidermal growth factor receptor 2 (HER2) receptors, which may slow the growth of cancer cells or cause some of the cells to die.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02122172

Sponsor: University of Chicago

Primary Outcome Measures:

  • Measure: Progression-free survival (PFS)
  • Time Frame: 3 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Overall response rate (CR + PR)
  • Time Frame: Up to 3 years
  • Safety Issue:
  • Measure: Median progression-free survival (PFS ) time
  • Time Frame: Up to 3 years
  • Safety Issue:
  • Measure: Overall survival
  • Time Frame: Up to 3 years
  • Safety Issue:
  • Measure: EGFR expression status
  • Time Frame: Baseline
  • Safety Issue:
  • Measure: HER2 expression status
  • Time Frame: Baseline
  • Safety Issue:

Estimated Enrollment: 95

Study Start Date: October 30, 2013

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Patients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatment
  • Patients must have histologically or cytologically confirmed urothelial tract carcinoma; patients with urothelial carcinoma of the bladder, upper tract, or urethra are eligible
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan for the evaluation of measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1])
  • Patients must have evidence of disease progression prior to enrollment
  • All patients must have received a prior platinum-based chemotherapy regimen for treatment of urothelial cancer and must now be considered refractory to platinum-based chemotherapy; patients may have received the platinum-containing regimen either in the peri-operative or metastatic setting
  • Patients may have received up to one line of prior systemic chemotherapy for recurrent/metastatic disease; if a platinum-based regimen was received both in the peri-operative setting and again in the metastatic setting, this will be considered 1 line of chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8.5g/dL
  • Total bilirubin =< 1.5 institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X IULN
  • Calculated creatinine clearance >= 30 mL/min by the modified Cockcroft and Gault Formula OR glomerular filtration rate >= 30 mL/min/body surface area (BSA) by Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
  • Women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients may not be receiving any other investigational agents
  • Patients with untreated known brain metastases, or treated brain metastases that are clinically unstable
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
  • Women known to be pregnant
  • Women who are breastfeeding and who are unwilling to stop breastfeeding prior to study entry
  • Patients with known prior human immunodeficiency virus (HIV)-positive status on combination antiretroviral therapy are ineligible; known prior HIV-positive patients with CD4+ =< 500/mm^3 are ineligible (HIV testing is not required as part of this study)
  • Pre-existing interstitial lung disease
  • Inability to take oral medications
  • Prior therapy with afatinib

Locations:

  • University of Chicago
  • Chicago Illinois 60637 United States
  • Decatur Memorial Hospital
  • Decatur Illinois 62526 United States
  • NorthShore University Health System
  • Evanston Illinois 60201 United States

View trial on ClinicalTrials.gov


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Prospective Study of Bladder-Preservation Chemo-Radiotherapy (Partial Bladder Hypo-fractionated Radiotherapy) for Patients With Muscle-Invasive Bladder Cancer


Condition: Infiltrating Bladder Urothelial Carcinoma

Intervention:

  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration

Purpose: This research trial studies quality of life after bladder-preservation chemotherapy and radiation therapy (chemo-radiotherapy) in patients with bladder cancer that has spread into or through the muscle layer of the bladder (muscle-invasive bladder cancer). Bladder-preservation chemo-radiotherapy is a standard treatment for patients with muscle-invasive bladder cancer, however, chemo-radiotherapy may cause urinary tract, bowel, and sexual late side effects that negatively affect patients' quality of life. Studying quality-of-life in patients with muscle-invasive bladder cancer after chemo-radiotherapy may help identify the long-term side effects of treatment and may help plan the best treatment in the future and improve patients' quality of life.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02688348

Sponsor: Jonsson Comprehensive Cancer Center

Primary Outcome Measures:

  • Measure: Establish QOL with validated tools for patients undergoing bladder-preservation chemo-radiation
  • Time Frame: From the date of study entry up to 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Quantify the rate of early and late grade 3 or higher GU or GI toxicity based on the CTCAE criteria
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Overall survival
  • Time Frame: From the date of study entry to the date of death, assessed up to 5 years
  • Safety Issue:

Estimated Enrollment: 50

Study Start Date: April 22, 2015

Eligibility:

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

Inclusion Criteria:

  • Histologically confirmed muscle-invasive urothelial cancer (no histology will be excluded)
  • No pelvic nodal metastases or distant metastases (based on computed tomography [CT], positron emission tomography [PET] or magnetic resonance imaging [MRI])
  • Karnofsky performance status (KPS) >= 70
  • Ability to understand, and willingness to sign, the written informed consent
  • Patient will have either opted for bladder-sparing treatment as compared to radical cystectomy, or deemed medically inoperable
  • Following the recent recommendations from the International Consultation on Urological Diseases-European Association of Urology International Consultation on Bladder Cancer, eligible patients will be those with no hydronephrosis, no extensive carcinoma in situ (CIS), and no tumor invasion into the stroma of the prostate

Exclusion Criteria:

  • Patients with any evidence of distant metastases
  • Prior pelvic radiotherapy
  • History of Crohn's disease or ulcerative colitis
  • Unable to receive chemotherapy
  • Histologies other than urothelial (eg. squamous cell carcinoma, adenocarcinoma, small cell)

Location:

  • UCLA / Jonsson Comprehensive Cancer Center
  • Los Angeles California 90095 United States

View trial on ClinicalTrials.gov


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PORCH: A Registry of Prospective Outcomes of Radical Cystectomy With or Without Chemotherapy


Condition: Bladder Cancer

Intervention:

  • Other: Collect Blood and Survey Instruments

Purpose: The purpose of this study is to create a registry of older patients undergoing surgical and/or medical treatment for bladder cancer. The registry will record side-effect and outcomes related to the treatment using different surveys and biological measures.

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT01776138

Sponsor: UNC Lineberger Comprehensive Cancer Center

Primary Outcome Measures:

  • Measure: To collect the number of changes in functional status, surgical complications and survival status collected in a prospective database of patients undergoing a radical cystectomy with or without chemotherapy
  • Time Frame: 1 Year
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: To measure associations between baseline measures with post-surgery and 90 day outcome measures
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: To count changes over the course of treatment for components of the GA, the FACT-Bl, p16, and other clinical characteristics.
  • Time Frame: 2 years
  • Safety Issue:

Estimated Enrollment: 150

Study Start Date: April 2012

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Eligibility:

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

Inclusion Criteria:

  • Patients with a known pathologic diagnosis of lower tract urothelial carcinoma who are eligible to undergo radical cystectomy with or without neoadjuvant chemotherapy for definitive diagnosis and treatment.
  • Signed, IRB approved written informed consent.
  • Completion of baseline Geriatric Assessment

Exclusion Criteria:

  • Inability to read and speak English
  • Inability to comply with study for any other reason than language
  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.

Contact:

  • Angie Smith, MD
  • (919) 966-8217

Location:

  • UNC Lineberger Comprehensive Cancer Center
  • Chapel Hill North Carolina 27514 United States

View trial on ClinicalTrials.gov


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A Phase II Study of Nivolumab Combined With Ipilimumab for Patients With Advanced Rare Genitourinary Tumors


Condition: Genitourinary Cancer, Adrenocortical Carcinoma, Non-urothelial Bladder, Non-urothelial Upper Tract, Penile Cancer, Non-adenocarcinoma Prostate Cancer, Refractory Germ-cell

Intervention:

  • Drug: Ipilimumab
  • Drug: Nivolumab

Purpose: This research study is studying a combination of drugs as a possible treatment for rare genitourinary malignancies. -The names of the study drugs involved in this study are: - Nivolumab - Ipilimumab

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03333616

Sponsor: Dana-Farber Cancer Institute

Primary Outcome Measures:

  • Measure: Objective Response Rate
  • Time Frame: Imaging will occur every 6-12 weeks study entry up until disease progression (up to 24 months)
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Objective Response Rate for all rare GU tumor types
  • Time Frame: Imaging will occur every 6-12 weeks study entry up until disease progression (up to 24 months)
  • Safety Issue:
  • Measure: Duration of Response
  • Time Frame: Imaging will occur every 6-12 weeks study entry up until disease progression (up to 24 months)
  • Safety Issue:
  • Measure: Immune related objective response rate
  • Time Frame: Imaging will occur every 6-12 weeks study entry up until disease progression (up to 24 months)
  • Safety Issue:
  • Measure: Progression-Free Survival for the total cohort and by tumor cohort
  • Time Frame: From start of treatment until date of death from any cause (average 24 months)
  • Safety Issue:
  • Measure: Overall Survival for all patients and by tumor cohort
  • Time Frame: From start of treatment until date of death from any cause. (Average 24 months)
  • Safety Issue:
  • Measure: Safety and tolerability according to Common Terminology Criteria for Adverse Events (CTCAE).
  • Time Frame: Throughout the course of the study, approximately 24 months after study entry.
  • Safety Issue:

Estimated Enrollment: 57

Study Start Date: December 28, 2017

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Age ≥ 18 years at the time of consent.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 within 28 days prior to registration (Appendix A).
  • Unresectable advanced or metastatic ACC, non-urothelial bladder/upper tract cancer, non-adenocarcinoma prostate cancer, penile cancer or treatment refractory germ-cell tumor. Pure is defined as >90% and those with a portion of urothelial carcinoma or prostate adenocarcinoma may be included at discretion of the principal investigator. With variant histology in the primary, if metastatic biopsy shows pure variant histology, patient is eligible
  • Availability of Formalin-fixed, Paraffin-embedded (FFPE) archival tumor specimens, when available, and willingness of the subject to undergo mandatory fresh tumor biopsy prior to treatment initiation unless determined medically unsafe or not feasible.
  • The archival specimen, when available, must contain adequate viable tumor tissue.
  • The specimen may consist of a tissue block (preferred and should contain the highest grade of tumor) or at least 20 unstained serial sections. Fine-needle aspiration, brushings, cell pellet from pleural effusion, bone marrow aspirate/biopsy are not acceptable.
  • A mandatory biopsy at the time of radiographic progression will be requested from patients who have an initial response to treatment and then subsequently progress as determined by RECIST version 1.1.
  • Measurable disease as defined by RECIST 1.1 within 28 days prior to registration.
  • Demonstrate adequate organ function. All screening labs to be obtained within 28 days prior to first study treatment.
  • Hematological
  • White blood cell (WBC) ≥ 2000 cells/µL
  • Absolute Neutrophil Count (ANC) ≥ 1000 cells/µL
  • Platelet count (plt) ≥ 75,000/ µL
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Absolute lymphocyte count ≥ 500 cells/µL
  • Renal
  • Serum creatinine OR
  • Calculated creatinine clearance1 ≤ 1.5 x ULN ≥ 40 mL/min
  • Hepatic and Other
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
  • AST2 ≤ 2.5 × ULN
  • ALT2 ≤ 2.5 × ULN
  • Alkaline Phosphatase2 ≤ 2.5 × ULN
  • Albumin > 2.5 g/dL
  • Coagulation
  • International Normalized Ratio (INR) or Prothrombin Time (PT)
  • Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin or warfarin)
  • Females of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
  • Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 120 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

Exclusion Criteria:

  • Prior use of systemic checkpoint inhibitors (including PD-1, PD-L1, and CTLA-4 targeting agents) for the management of ACC, non-urothelial bladder cancer/upper tract, non-adenocarcinoma prostate cancer, penile cancer or treatment refractory germ-cell tumor is excluded
  • Treatment with systemic immunosuppressive medications including but not limited to: prednisone, dexamethasone, cyclosporine, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor (TNF) agents within 2 weeks of first study dose.
  • Subjects who have received acute, low-dose systemic immunosuppressant medications may be enrolled (such as steroids for acute nausea or cancer-related pain ≤ 10 mg prednisone) maybe enrolled sooner than 2 weeks of first study dose.
  • Subjects with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled (≤ 10 mg prednisone).
  • The use of inhaled, topical, ocular or intra-articular corticosteroids and mineralocorticoids are allowed.
  • Treatment with chemotherapy, hormone therapy, or other investigational therapy within 3 weeks of first study doses. Patients with non-adenocarcinoma of the prostate who may be on luteinizing hormone-releasing hormone agonist/antagonist therapy may continue use. For ACC patients, hormonal agents (e.g mitotane) are allowed for the purpose to control endocrine-related symptoms when needed.
  • Radiotherapy within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
  • Known active metastases to the brain, spinal cord or leptomeninges. Patients who are treated with radiotherapy, radiosurgery, or surgery and clinically stable for at least 2 weeks of first study treatment are eligible. Repeat imaging is not required to document treatment response.
  • Malignancies other than ACC, non-urothelial bladder/upper tract cancer, non-adenocarcinoma prostate cancer, penile cancer or treatment refractory germ-cell tumor within 5 years of first study treatment with the exception of those with negligible risk of metastases or death and/or treated with expected curative outcome (included but not limited to carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer for patients with malignancies other than non-adenocarcinoma of the prostate, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma of the bladder for patients with malignancies other than non-urothelial bladder cancer).
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
  • Known hypersensitivity to any component of the nivolumab or ipilimumab product.
  • Any active or recent history (within 6 months of first study dose) of autoimmune disease or syndrome that requires systemic corticosteroids (>10 mg daily prednisone equivalent) or immunosuppressive medications including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Subjects with vitiligo, controlled type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement therapy are permitted to enroll.
  • Any condition requiring treatment with corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medication within 14 days of the first dose of study drug. Inhaled, topical, ocular or intra-articular corticosteroids and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Uncontrolled adrenal insufficiency.
  • History of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening imaging CT of the chest. History of radiation pneumonitis in the radiation field is permitted.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
  • Active or chronic hepatitis B infection (defined as having a positive hepatitis B surface antigen (HBsAg) test at screening). Subject with past or resolved hepatitis B infection (defined as having a negative HBsAg test and positive antibody to hepatitis B core antigen test) are eligible. Hepatitis B viral DNA must be obtained in Subjects with positive hepatitis B core antibody prior to first treatment start.
  • Active hepatitis C infection. Subjects positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
  • Receipt of therapeutic oral or IV antibiotics within 2 weeks of first study treatment. Subjects receiving routine antibiotic prophylaxis (for dental extractions/procedures) are eligible.
  • Significant cardiovascular disease such New York Heart Association (NYHA) class III or greater, myocardial infarction within the previous 3 months, unstable arrhythmias, unstable angina, need for cardiac angioplasty or stenting, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease. Subjects with known coronary artery disease treated with stenting or coronary artery by-pass graft, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate.
  • Prolongation of the QTcF interval defined as > 450 msec for males and > 470 msec for females.
  • Inadequately controlled hypertension (defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg). Anti-hypertensive therapy to achieve these parameters is allowed.
  • History of cerebrovascular accident or transient ischemic attack within 3 months of first study dose.
  • Significant vascular disease (such as aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 3 months of first study dose.
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) within 4 weeks of first study dose.
  • History of symptomatic deep vein thrombosis or pulmonary embolism within 4 weeks of first study dose.
  • History of abdominal or tracheoesophageal fistula or GI perforation within 6 months of first study treatment.
  • Clinical signs or symptoms of GI obstruction or requirement of routine parenteral nutrition or tube feedings.
  • Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
  • Serious, non-healing or dehiscing wound or active ulcer.
  • Major surgical procedure within 4 weeks of first study treatment.
  • Presence of any toxicities attributed to prior anti-cancer therapy that are not resolved to grade 2 (CTCAE version 4.0) or baseline that could impose risk for serious complications before administration of study drug,
  • Prior allogenic stem cell or solid organ transplant.

Contact:

  • Deanna M Hart
  • 617-582-7334

Locations:

  • University of California, San Diego Moores Cancer Center
  • La Jolla California 92093 United States
  • Winship Cancer Institute, Emory University
  • Atlanta Georgia 30322 United States
  • Beth Israel Deaconess Medical Center
  • Boston Massachusetts 02115 United States
  • Dana-Farber Cancer Institute
  • Boston Massachusetts 02115 United States
  • Ohio State University Comprehensive Cancer Center
  • Columbus Ohio 43210 United States
  • MD Anderson Cancer Center
  • Houston Texas 77030 United States

View trial on ClinicalTrials.gov


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A Phase 3, Randomized, Study of Neoadjuvant Chemotherapy Alone Versus Neoadjuvant Chemotherapy Plus Nivolumab or Nivolumab and BMS-986205, Followed by Continued Post- Surgery Therapy With Nivolumab or Nivolumab and BMS-986205 in Participants With Muscle- Invasive Bladder Cancer


Condition: Bladder Cancer, Muscle-Invasive Bladder Cancer, BMS-986205

Intervention:

  • Biological: Nivolumab
  • Drug: BMS-986205
  • Drug: Gemcitabine
  • Drug: Cisplatin
  • Drug: BMS-986205 Placebo

Purpose: A study to evaluate nivolumab + chemotherapy or nivolumab/ BMS-986205 + chemotherapy followed by continued Immuno-Oncology therapy after radical cystectomy (RC) compared with neoadjuvant standard of care (SOC) chemotherapy alone in patients with muscle-invasive bladder cancer (MIBC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03661320

Sponsor: Bristol-Myers Squibb

Primary Outcome Measures:

  • Measure: Pathological Complete Response (pCR) rate, in all treated participants, based on blinded pathology review.
  • Time Frame: Approx. 39 months
  • Safety Issue:
  • Measure: Event-Free Survival (EFS), in all treated participants, based on BIRC assessments, or death due to any cause.
  • Time Frame: Approx. 57 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Overall Survival (OS) in all treated participants
  • Time Frame: Approx. 76 months
  • Safety Issue:
  • Measure: Incidence of Adverse Events (AE) in all treated participants
  • Time Frame: Approx. 76 months
  • Safety Issue:
  • Measure: Incidence of Serious Adverse Events (SAE) in all treated participants
  • Time Frame: Approx. 76 months
  • Safety Issue:
  • Measure: Incidence of Laboratory abnormalities in all treated participants
  • Time Frame: Approx. 76 months
  • Safety Issue:
  • Measure: Pathological Complete Response (pCR) rate, in all treated participants, based on blinded pathology review.
  • Time Frame: Approx. 39 months
  • Safety Issue:
  • Measure: Event Free Survival (EFS), in all treated participants, based on BIRC assessments, or death due to any cause.
  • Time Frame: Approx. 57 months
  • Safety Issue:

Estimated Enrollment: 1200

Study Start Date: October 12, 2018

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Participants with MIBC, clinical stage T2-T4a, N0 (<10 mm on CT or MRI), M0, diagnosed at TURBT and confirmed by radiographic imaging. Variant histology is acceptable if there is a predominant urothelial component.
  • Participant must be deemed eligible for Radial Cystectomy (RC) by his/her oncologist and/or urologist, and must agree to undergo Radial Cystectomy (RC) after completion of neoadjuvant therapy.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

Exclusion Criteria:

  • Clinical evidence of positive LN (≥ 10 mm in short axis) or metastatic bladder cancer
  • Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than TURBT or biopsies is also not permitted
  • Ineligible to receive cisplatin due to Grade 2 or higher peripheral neuropathy or audiometric hearing loss, or calculated (Cockcroft-Gault formula) GFR or measured (24-hour urine) creatinine clearance (CrCl) < 50 mL/min

Contact:

  • Recruiting sites have contact information. Please contact the sites directly. If there is no contact information
  • please email:

Locations:

  • Local Institution
  • Mobile Alabama 36608 United States
  • Local Institution
  • Chandler Arizona 85224 United States
  • Arizona Oncology Associates
  • Tucson Arizona 85711 United States
  • Local Institution
  • Irvine California 92868 United States
  • Local Institution
  • La Jolla California 92093-0987 United States
  • Local Institution
  • Sacramento California 95817 United States
  • Local Institution
  • San Jose California 95124 United States
  • Rocky Mountain Cancer Centers Llp
  • Littleton Colorado 80120-4413 United States
  • Local Institution
  • New Haven Connecticut 06520 United States
  • Local Institution
  • Newark Delaware 19713 United States
  • Woodlands Medical Specialists, Pa
  • Pensacola Florida 32503 United States
  • Local Institution
  • Tampa Florida 33612-9416 United States
  • Local Institution
  • Atlanta Georgia 30342 United States
  • The University Of Chicago
  • Chicago Illinois 60637 United States
  • Local Institution
  • Peoria Illinois 61615 United States
  • Local Institution
  • Baltimore Maryland 21201 United States
  • Local Institution
  • Columbia Maryland 21044 United States
  • Local Institution
  • Boston Massachusetts 02215 United States
  • Local Institution
  • Boston Massachusetts 02215 United States
  • Minnesota Oncology Hematology
  • Minneapolis Minnesota 55404 United States
  • Local Institution
  • Minneapolis Minnesota 55455 United States
  • Local Institution
  • Omaha Nebraska 68198-6840 United States
  • Local Institution
  • Omaha Nebraska 68310 United States
  • Comprehensive Cancer Centers Of Nevada
  • Las Vegas Nevada 89169 United States
  • Local Institution
  • Camden New Jersey 08103 United States
  • New York Oncology Hematology, Pc
  • Albany New York 12208 United States
  • Local Institution
  • Lake Success New York 11042 United States
  • Columbia University Medical Center (Cumc)
  • New York New York 10032 United States
  • Local Institution
  • Cleveland Ohio 44195 United States
  • Northwest Cancer Specialists, Pc
  • Tualatin Oregon 97062 United States
  • Local Institution
  • Charleston South Carolina 29425 United States
  • Local Institution
  • Nashville Tennessee 37232 United States
  • Texas Oncology, PA - Central Austin Cancer Center
  • Austin Texas 78731 United States
  • Local Institution
  • Dallas Texas 75390 United States
  • Local Institution
  • Fort Sam Houston Texas 78234 United States
  • Virginia Oncology Associates
  • Norfolk Virginia 23502 United States
  • Local Institution
  • Capital Federal Buenos Aires 1426 Argentina
  • Local Institution
  • Ciudad Autonoma Buenos Aires Buenos Aires 1118 Argentina
  • Local Institution
  • Ciudad Autónoma de Buenos Aires Buenos Aires 1280 Argentina
  • Local Institution
  • Garran Australian Capital Territory 2605 Australia
  • Local Institution
  • Kingswood New South Wales 2747 Australia
  • Local Institution
  • Macquarie Park New South Wales 2109 Australia
  • Local Institution
  • St Leonards New South Wales 2065 Australia
  • Local Institution
  • North Adelaide South Australia 5006 Australia
  • Local Institution
  • Heidelberg Victoria 3084 Australia
  • Local Institution
  • Murdoch 6150 Australia
  • Local Institution
  • Klagenfurt Am Woerthersee 9020 Austria
  • Local Institution
  • Krems 3500 Austria
  • Krankenhaus der Elisabethinen Linz GmbH
  • Linz 4010 Austria
  • AKH Allgemeines Krankenhaus Wien
  • Wien 1090 Austria
  • Local Institution
  • Antwerpen 2018 Belgium
  • Local Institution
  • Bruxelles 1200 Belgium
  • Local Institution
  • Gent 9000 Belgium
  • Local Institution
  • Leuven B-300 Belgium
  • Local Institution
  • Fortaleza Ceara 60130-241 Brazil
  • Local Institution
  • Ipatinga Minas Gerais 35160-158 Brazil
  • Local Institution
  • Ijui RIO Grande DO SUL 98700-000 Brazil
  • Local Institution
  • Porto Alegre RIO Grande DO SUL 90610-000 Brazil
  • Local Institution
  • Barretos SAO Paulo 14780-070 Brazil
  • Local Institution
  • Jau SAO Paulo 17210-080 Brazil
  • Local Institution
  • Sao Jose Do Rio Preto SAO Paulo 15090-000 Brazil
  • Local Institution
  • Rio De Janeiro 20231-050 Brazil
  • Local Institution
  • Sao Paulo 01246-000 Brazil
  • Local Institution
  • Abbotsford British Columbia V2S 0C2 Canada
  • Local Institution
  • Kelowna British Columbia V1Y 5L3 Canada
  • Local Institution
  • North York Ontario M2K 1E1 Canada
  • Local Institution
  • Chicoutimi Quebec G7H 5H6 Canada
  • Local Institution
  • Montreal Quebec H3T 1M5 Canada
  • Local Institution
  • Santiago Metropolitana 8330024 Chile
  • Local Institution
  • Santiago Metropolitana Chile
  • Local Institution
  • Independencia Santiago Chile
  • Local Institution
  • Monteria 230003 Colombia
  • Local Institution
  • Santander Colombia
  • Local Institution
  • ?lborg 9000 Denmark
  • Local Institution
  • Arhus 8000 Denmark
  • Local Institution
  • Herlev 2730 Denmark
  • Local Institution
  • Helsinki 00029 Finland
  • Local Institution
  • Tampere 33521 Finland
  • Local Institution
  • Turku 20521 Finland
  • Local Institution
  • Besancon 25030 France
  • Local Institution
  • Bordeaux 33075 France
  • Local Institution
  • Marseille 13273 France
  • Local Institution
  • Nice 06189 France
  • Local Institution
  • Paris 75014 France
  • Local Institution
  • Pierre Benite 69310 France
  • Local Institution
  • Rennes Cedex 35042 France
  • Local Institution
  • Saint Herblain Cedex 44805 France
  • Local Institution
  • Strasbourg Cedex 67091 France
  • Local Institution
  • TOULOUSE Cedex 9 31059 France
  • Local Institution
  • Aachen 52074 Germany
  • Local Institution
  • Erfurt 99028 Germany
  • Local Institution
  • Essen 45136 Germany
  • Local Institution
  • Frankfurt Main 60590 Germany
  • Local Institution
  • Goettingen 37075 Germany
  • Local Institution
  • Heidelberg 69120 Germany
  • Marien Hospital Herne
  • Herne 44625 Germany
  • Universitaetsklinikum Jena
  • Jena 07747 Germany
  • Local Institution
  • Luebeck 23538 Germany
  • Local Institution
  • Magdeburg 39120 Germany
  • Local Institution
  • Mainz 55101 Germany
  • Local Institution
  • Muenchen 81675 Germany
  • Local Institution
  • Nuernberg 90419 Germany
  • Local Institution
  • Trier 54292 Germany
  • Local Institution
  • Athens 11528 Greece
  • Local Institution
  • Larissa 41110 Greece
  • Local Institution
  • Beer Sheva 84101 Israel
  • Local Institution
  • Haifa 3109601 Israel
  • Local Institution
  • Ramat Gan 52621 Israel
  • Local Institution
  • Bari 70124 Italy
  • Local Institution
  • Milano 20133 Italy
  • Local Institution
  • Modena 41012 Italy
  • Local Institution
  • Padova 35128 Italy
  • Local Institution
  • Pisa 56126 Italy
  • Local Institution
  • Roma 00168 Italy
  • Local Institution
  • Komaki-shi Aichi 485-8520 Japan
  • Local Institution
  • Fukuoka-shi Fukuoka 8128582 Japan
  • Local Institution
  • Sapporo-shi Hokkaido 0030804 Japan
  • Local Institution
  • Sapporo-shi Hokkaido 0608543 Japan
  • Local Institution
  • Sapporo-shi Hokkaido 0608604 Japan
  • Local Institution
  • Tsukuba-shi Ibaraki 3058576 Japan
  • Local Institution
  • Yokohama-shi Kanagawa 2220036 Japan
  • Local Institution
  • Niigata-shi Niigata 9518520 Japan
  • Local Institution
  • Osaka-sayama-shi Osaka 5898511 Japan
  • Local Institution
  • Takatsuki-shi Osaka 5698686 Japan
  • Local Institution
  • Hidaka-shi Saitama 3501298 Japan
  • Local Institution
  • Hamamatsu-shi Shizuoka 4313192 Japan
  • Local Institution
  • Minato-ku Tokyo 1058470 Japan
  • Local Institution
  • Shinjuku-Ku Tokyo 1608582 Japan
  • Local Institution
  • Kita-gun 7610793 Japan
  • Local Institution
  • Kyoto 6068507 Japan
  • Local Institution
  • Goyang-si Gyeonggi-do 10408 Korea, Republic of
  • Local Institution
  • Seoul 02841 Korea, Republic of
  • Local Institution
  • Seoul 03080 Korea, Republic of
  • Local Institution
  • Seoul 06351 Korea, Republic of
  • Local Institution
  • La Paz BAJA Californa SUR 23040 Mexico
  • Local Institution
  • Df Distrito Federal 06720 Mexico
  • Local Institution
  • Zapopan Jalisco 45050 Mexico
  • Local Institution
  • Monterrey Nuevo LEON 64460 Mexico
  • Local Institution
  • Colima 28018 Mexico
  • Local Institution
  • Amsterdam 1066 CX Netherlands
  • Local Institution
  • Groningen 9713 GZ Netherlands
  • Local Institution
  • Heerlen 6419 PC Netherlands
  • Local Institution
  • Auckland 1023 New Zealand
  • Local Institution
  • Christchurch 8011 New Zealand
  • Local Institution
  • Gralum 1714 Norway
  • Local Institution
  • Lorenskog 1478 Norway
  • Local Institution
  • Oslo 0383 Norway
  • Local Institution
  • Lisboa 1649-035 Portugal
  • Local Institution
  • Porto 4200-072 Portugal
  • Local Institution
  • Bucharest 020122 Romania
  • Local Institution
  • Craiova 200347 Romania
  • Local Institution
  • Saint-Petersburg 194044 Russian Federation
  • Local Institution
  • Saint-Petersburg 197758 Russian Federation
  • Local Institution
  • Singapore 169610 Singapore
  • Local Institution
  • Lugo 27003 Spain
  • Local Institution
  • Madrid 28007 Spain
  • Local Institution
  • Madrid 28033 Spain
  • Local Institution
  • Madrid 28041 Spain
  • Local Institution
  • Malaga 29010 Spain
  • Local Institution
  • Sevilla 41013 Spain
  • Local Institution
  • Kaohsiung 883 Taiwan
  • Local Institution
  • Taichung 40705 Taiwan
  • Local Institution
  • Taipei 10048 Taiwan
  • Local Institution
  • Taipei 11217 Taiwan
  • Local Institution
  • Chelmsford Essex CM1 7ET United Kingdom
  • Local Institution
  • York Yorkshire YO31 8HE United Kingdom
  • Local Institution
  • Glasgow G12 0YN United Kingdom
  • Local Institution
  • Lancaster LA1 4RP United Kingdom
  • Local Institution
  • London SE1 9RT United Kingdom
  • Local Institution
  • Oxford OX3 7LE United Kingdom

View trial on ClinicalTrials.gov


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