Urothelial Carcinoma Clinical Trial
Official title:
A Phase 2 Study of Sitravatinib in Combination With PD-(L)1 Checkpoint Inhibitor Regimens in Patients With Advanced or Metastatic Urothelial Carcinoma
Verified date | August 2023 |
Source | Mirati Therapeutics Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The study will evaluate the clinical activity of PD-(L)1 Checkpoint Inhibitor regimens in combination with the investigational agent sitravatinib in patients with advanced or metastatic urothelial carcinoma.
Status | Terminated |
Enrollment | 260 |
Est. completion date | August 22, 2022 |
Est. primary completion date | August 3, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Diagnosis of urothelial carcinoma - Adequate bone marrow and organ function Exclusion Criteria: - Uncontrolled tumor in the brain - Unacceptable toxicity with prior checkpoint inhibitor - Impaired heart function |
Country | Name | City | State |
---|---|---|---|
United States | New York Oncology Hematology - Albany Medical Center | Albany | New York |
United States | Rocky Mountain Cancer Centers | Aurora | Colorado |
United States | Texas Oncology-Austin Central | Austin | Texas |
United States | Dana Farber Cancer Institute | Boston | Massachusetts |
United States | Roswell Park Cancer Institute | Buffalo | New York |
United States | University of North Carolina - Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina |
United States | The University of Chicago | Chicago | Illinois |
United States | The Ohio State University College of Medicine | Columbus | Ohio |
United States | Barbara Ann Karmanos Cancer Institute | Detroit | Michigan |
United States | Duke University Hospital | Durham | North Carolina |
United States | Virginia Cancer Specialists- Fairfax | Fairfax | Virginia |
United States | Texas Oncology- Memorial City | Houston | Texas |
United States | University of Texas - MD Anderson Cancer Center | Houston | Texas |
United States | Indiana University - Melvin & Bren Simon Cancer Center | Indianapolis | Indiana |
United States | University of California Irvine | Irvine | California |
United States | Northwell Health Monter Cancer Center | Lake Success | New York |
United States | Maryland Oncology Hematology, P.A. | Lanham | Maryland |
United States | Comprehensive Cancer Centers of Nevada - Southwest | Las Vegas | Nevada |
United States | Norton Cancer Institute - Broadway | Louisville | Kentucky |
United States | Vanderbilt University - Ingram Cancer Center | Nashville | Tennessee |
United States | Yale School of Medicine | New Haven | Connecticut |
United States | Ochsner Cancer Institute | New Orleans | Louisiana |
United States | Memorial Sloan-Kettering Cancer Center | New York | New York |
United States | New York-Presbyterian - Weill Cornell Medical Center | New York | New York |
United States | NYU Langone Laura & Isaac Perlmutter Cancer Center | New York | New York |
United States | Virginia Oncology Associates | Norfolk | Virginia |
United States | GU Research Network/Urology Cancer Center | Omaha | Nebraska |
United States | Allegheny General Hospital | Pittsburgh | Pennsylvania |
United States | Washington University School of Medicine - Siteman Cancer Center | Saint Louis | Missouri |
United States | SCRI - Florida Cancer Specialists- North Region | Saint Petersburg | Florida |
United States | University of Texas Health Science Center | San Antonio | Texas |
United States | Seattle Cancer Center Alliance | Seattle | Washington |
United States | Moffitt Cancer Center | Tampa | Florida |
United States | The University of Arizona Cancer Center | Tucson | Arizona |
United States | Texas Oncology - Tyler | Tyler | Texas |
United States | SCRI - Florida Cancer Specialists - West Palm Beach | West Palm Beach | Florida |
Lead Sponsor | Collaborator |
---|---|
Mirati Therapeutics Inc. |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Objective Response Rate (ORR) | ORR was defined as the number of participants documented to have a confirmed investigator-assessed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. | Up to approximately 3 years | |
Secondary | Number of Participants Who Experienced an Adverse Event (AE) | An AE was defined as any reaction, side effect or other undesirable medical event that occurred during participation in a clinical trial, regardless of treatment group or suspected causal relationship to study treatment. Any clinically significant changes from baseline in laboratory results were recorded as AEs. | Day 1 up to approximately 3 years | |
Secondary | Number of Participants Who Experienced a Serious Adverse Event (SAE) | An SAE was defined as any event that resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/permanent damage (substantial disruption of the ability to conduct normal life functions), a congenital anomaly/birth defect, or may have jeopardized the participant and may have required medical or surgical intervention to prevent intensive treatment in an emergency room or at home (e.g. for allergic bronchospasm, blood dyscrasias or convulsions) that do not result in inpatient hospitalization, development of drug dependency or drug abuse. | Day 1 up to approximately 3 years | |
Secondary | Number of Participants Who Experienced a Treatment-related Adverse Event | A treatment-related adverse event was defined as an adverse event determined to have a possible causal relationship to the study treatment(s) by the investigator. An adverse event was defined as any reaction, side effect or other undesirable medical event that occurred during participation in a clinical trial. Any clinically significant changes from baseline in laboratory results were recorded as adverse events. | Day 1 up to approximately 3 years | |
Secondary | Duration of Response (DOR) | DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of objective progression of disease (PD) per RECIST V1.1, or to death due to any cause in the absence of documented PD. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare efficacy endpoints across Cohort 9 dose levels. |
Up to approximately 3 years | |
Secondary | Clinical Benefit Rate (CBR) | Clinical Benefit Rate (CBR) was defined as the number of participants documented to have a confirmed CR, PR, or stable disease (SD), per RECIST V1.1, documented during at least 1 on-study assessment. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. SD was defined as target lesions increasing by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds. | Up to approximately 3 years | |
Secondary | Progression-Free Survival (PFS) | PFS was defined as the time from date of first study treatment to first PD per RECIST V1.1, or death due to any cause in the absence of documented PD. | Up to approximately 3 years | |
Secondary | 1-Year Survival Rate | Survival was defined as the time from date of first study treatment to death due to any cause. Kaplan-Meier (product limit) estimates of the percentage of participants who died at 1-year was calculated to estimate the 1-year survival rate, defined as the percentage of participants alive at 1 year. Confidence Intervals were calculated based on Greenwood's formula. Participants who discontinued prior to 1-year were censored on the last date that they were known to be alive. For participants with no follow-up after first dose of study drug, survival rate was censored at the date of first dose (Day 1). | 1 year | |
Secondary | Overall Survival (OS) | OS was defined as the time from date of first study treatment to death due to any cause. | Up to approximately 3 years | |
Secondary | Geometric Mean Blood Plasma Concentration of Sitravatinib | Blood draws for analysis of blood plasma concentrations of sitravatinib were collected following electrocardiograms and assessment of vital signs. Concentration data below the limit of quantification were set to 0. | Cycle(C)1 Day(D)1 pre-dose, 30min, 2,4,6,7,8,24hr post-dose, C1D15 pre-dose, 30min,2,4,6,7,8,24hr post-dose, C2D1 pre-dose,7hr post-dose, C2D8,C3D1,C3D8,C5D1,C6D8 pre-dose (28 day cycles Cohorts 1-8, 21 day cycles Cohort 9) | |
Secondary | Cohort 9 Lead-in Dose Escalation Part Only: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) | A DLT was defined as any of the following events considered to be causally related to treatment with sitravatinib in combination with pembrolizumab and enfortumab in the lead-in dose escalation part of Cohort 9 (as pre-specified): hematological DLTs (Grade 4 neutropenia, thrombocytopenia, anemia unexplained by underlying disease, =Grade 3 febrile neutropenia or neutropenia with significant clinical sequelae, or any requirement for a platelet transfusion), non-hematological DLTs (=Grade 4 infusion related reaction, non-hematological toxicity, Grade 3 infusion related reaction that does not resolve within 24 hours, hypertension that cannot be controlled with medical therapy), other Grade 3 non-hematologic toxicity lasting for >3 days, with exceptions, Grade 2 pneumonitis or colitis, =Grade 3 non-hematological laboratory abnormalities, alanine transaminase>3 x upper limit of normal (ULN) with bilirubin> 2xULN, and other related toxic effects may have been assessed as DLTs. | Cycle 1 Day 1 through pre-dose Cycle 2 Day 1 (cycle for Cohort 9 was 21 days) |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT03170960 -
Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04242199 -
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors
|
Phase 1 | |
Completed |
NCT03520231 -
Study Comparing Denosumab With Standard Treatment in Urothelial Cancer Patients With Bone Metastases
|
Phase 2 | |
Recruiting |
NCT05775874 -
A Study to Evaluate the Safety and Efficacy of AZD4547 Combination With Tislelizumab in Patients With mUC
|
Phase 2 | |
Recruiting |
NCT04623502 -
An Investigation of Kidney and Urothelial Tumor Metabolism in Patients Undergoing Surgical Resection and/or Biopsy
|
N/A | |
Recruiting |
NCT04617756 -
Safety & Efficacy of Durvalumab+Neoadjuvant Chemotherapy for High-risk Urothelial Carcinoma of the Upper Urinary Tract
|
Phase 2 | |
Recruiting |
NCT06116396 -
Liquid Biospy for Urinary Cancers
|
||
Recruiting |
NCT05723991 -
Study of Disitamab Vedotin Combined With Gemcitabine in Neoadjuvant Treatment of Urothelial Carcinoma
|
Phase 4 | |
Active, not recruiting |
NCT03039413 -
Copper Cu-64 TP3805 PET/CT in Imaging Patients With Urothelial Cancer Undergoing Surgery or Biopsy
|
Early Phase 1 | |
Completed |
NCT02795156 -
Study Assessing Activity of Molecularly Matched Targeted Therapies in Select Tumor Types Based on Genomic Alterations
|
Phase 2 | |
Terminated |
NCT03915405 -
KHK2455 (IDO Inhibitor) Plus Avelumab in Adult Subjects With Advanced Bladder Cancer
|
Phase 1 | |
Completed |
NCT03980041 -
Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
|
Phase 2 | |
Completed |
NCT04452214 -
A Study of the Safety and Tolerance of CAN04 and Pembrolizumab in Combination With and Without Carboplatin and Pemetrexed in Subjects With Solid Tumors
|
Phase 1 | |
Completed |
NCT03652077 -
A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies
|
Phase 1 | |
Recruiting |
NCT05911295 -
Disitamab Vedotin With Pembrolizumab vs Chemotherapy in Previously Untreated Urothelial Cancer Expressing HER2
|
Phase 3 | |
Terminated |
NCT01093066 -
Prospective Multicentric Evaluation of a Bladder Preservation Strategy
|
Phase 2 | |
Terminated |
NCT01042795 -
Trial of Adjuvant Sutent for Patients With High Risk Urothelial Carcinoma After Neoadjuvant Chemotherapy and Cystectomy
|
Phase 2 | |
Recruiting |
NCT06022757 -
Study of XNW5004 Tablet in Combination With KEYTRUDA® (Pembrolizumab) in Subjects With Advanced Solid Tumors Who Failed Standard Treatments (KEYNOTE F19)
|
Phase 1/Phase 2 | |
Recruiting |
NCT03212404 -
Phase 1 Study of CK-301 (Cosibelimab) as a Single Agent in Subjects With Advanced Cancers
|
Phase 1 | |
Recruiting |
NCT04140526 -
Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC
|
Phase 1/Phase 2 |