Bladder Cancer

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


Condition: Bladder Cancer

Intervention:

  • Drug: Pembrolizumab (MK-3475)

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03504163

Sponsor: Memorial Sloan Kettering Cancer Center

Primary Outcome Measures:

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

Estimated Enrollment: 37

Study Start Date: June 27, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

Contact:

  • Dean Bajorin, MD
  • 646-422-4333

Location:

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

View trial on ClinicalTrials.gov


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


Condition: Urothelial Carcinoma

Intervention:

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

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03502785

Sponsor: Inovio Pharmaceuticals

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment: 85

Study Start Date: May 24, 2018

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

Contact:

  • Inovio Call Center
  • 267-440-4237

Locations:

  • Alaska Clinical Research Center, LLC
  • Anchorage Alaska 99503 United States
  • Indiana University Simon Cancer Center
  • Indianapolis Indiana 46202 United States
  • Karmanos Cancer Institute
  • Detroit Michigan 48201 United States
  • Washington University School of Medicine in St. Louis
  • Saint Louis Missouri 63110 United States
  • Columbia University, Herbert Irving Comprehensive Cancer Center
  • New York New York 10032 United States
  • University of Pittsburgh Medical Center
  • Pittsburgh Pennsylvania 15232 United States
  • Greenville Memorial Hospital
  • Greenville South Carolina 29615 United States

View trial on ClinicalTrials.gov


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


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

Intervention:

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

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03609216

Sponsor: Alliance for Clinical Trials in Oncology

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment: 271

Study Start Date: August 1, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

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

Eligibility Criteria:

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

Contact:

  • Gopa Iyer, MD
  • 646-888-4737

Locations:

  • Iowa Methodist Medical Center
  • Des Moines Iowa 50309 United States
  • Medical Oncology and Hematology Associates-Des Moines
  • Des Moines Iowa 50309 United States
  • Broadlawns Medical Center
  • Des Moines Iowa 50314 United States
  • Iowa Lutheran Hospital
  • Des Moines Iowa 50316 United States
  • Trinity Regional Medical Center
  • Fort Dodge Iowa 50501 United States
  • Methodist West Hospital
  • West Des Moines Iowa 50266-7700 United States
  • East Jefferson General Hospital
  • Metairie Louisiana 70006 United States
  • Louisiana State University Health Science Center
  • New Orleans Louisiana 70112 United States
  • Alliance for Clinical Trials in Oncology
  • Boston Massachusetts 02115 United States

View trial on ClinicalTrials.gov


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


Condition: Advanced or Metastatic Solid Tumor

Intervention:

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

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03517956

Sponsor: Bayer

Primary Outcome Measures:

  • Measure: Incidence of treatment-emergent adverse events (TEAEs)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of drug-related TEAEs
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of treatment-emergent serious adverse events (TESAEs)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of Dose-limiting toxicities (DLTs)
  • Time Frame: Approximately 10 months
  • Safety Issue:

Secondary Outcome Measures:

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

Estimated Enrollment: 65

Study Start Date: July 25, 2018

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • High FGFR mRNA expression levels (RNAscope score of 3+ or 4+; measurement is part of this protocol) in archival or fresh tumor biopsy specimen.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in contrast enhanced (unless contraindicated) CT or MRI.
  • Adequate bone marrow, liver and renal function.
  • Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) formula.
  • Left ventricular ejection fraction (LVEF) equal to or above the lower limit of normal (LLN) at the institution.
  • Life expectancy of at least 3 months.
  • For the dose escalation part: Patients with histologically confirmed, locally advanced or metastatic solid tumors who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anti-cancer treatment is no longer effective, excluding primary brain or spinal tumors.
  • For the dose expansion part: Patients with histologically confirmed, locally advanced or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anticancer treatment is no longer effective.

Exclusion Criteria:

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

Contact:

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

Locations:

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

View trial on ClinicalTrials.gov


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


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

Intervention:

  • Drug: Sitravatinib
  • Drug: Nivolumab

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03606174

Sponsor: Mirati Therapeutics Inc.

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment: 80

Study Start Date: September 11, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

Contact:

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

Locations:

  • Washington University in St Louis
  • Saint Louis Missouri 63110 United States
  • GU Research Network/Urology Cancer Center
  • Omaha Nebraska 68130 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89169 United States
  • New York Oncology Hematology
  • Albany New York 12206 United States
  • Texas Oncology-Austin Central
  • Austin Texas 78731 United States
  • Texas Oncology- Memorial City
  • Houston Texas 77024 United States
  • Texas Oncology - Tyler
  • Tyler Texas 75702 United States
  • Virginia Cancer Specialists- Fairfax
  • Fairfax Virginia 22031 United States

View trial on ClinicalTrials.gov


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


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

Intervention:

  • Drug: IMCnyeso
  • Drug: IMCnyeso

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03515551

Sponsor: Immunocore Ltd

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment: 63

Study Start Date: May 1, 2018

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

Contact:

  • Rachael Easton, MD, PhD
  • 484-434-5261

Location:

  • Hillman Cancer Center
  • Pittsburgh Pennsylvania 15232 United States

View trial on ClinicalTrials.gov


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


Condition: Non-metastatic Muscle Invasive Bladder Cancer

Intervention:

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

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03674424

Sponsor: Jules Bordet Institute

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment: 196

Study Start Date: June 1, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

Locations:

  • Institut Jules Bordet
  • Brussels 1000 Belgium
  • CHU de Liège Sart Tilman
  • Liège 4000 Belgium

View trial on ClinicalTrials.gov


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