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Trial record 1 of 1 for:    NCT03606174
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Study of Sitravatinib and Nivolumab in Urothelial Carcinoma

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ClinicalTrials.gov Identifier: NCT03606174
Recruitment Status : Recruiting
First Posted : July 30, 2018
Last Update Posted : March 2, 2020
Sponsor:
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE July 20, 2018
First Posted Date  ICMJE July 30, 2018
Last Update Posted Date March 2, 2020
Actual Study Start Date  ICMJE September 11, 2018
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
Number of patients experiencing tumor size reduction [ Time Frame: duration of study ]
overall response rate by RECISTv1.1
Original Primary Outcome Measures  ICMJE
 (submitted: July 20, 2018)
Number of patients experiencing tumor size reduction [ Time Frame: up to 3 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
  • Number of patients experiencing adverse events [ Time Frame: duration of study ]
    characterization of adverse events by incidence, severity, timing, seriousness & relationship to study treatment
  • Blood plasma concentration of the investigational agent [ Time Frame: duration of study ]
    Blood plasma concentration of the investigational agent
  • characterization of patients experiencing tumor size reduction [ Time Frame: 12 months ]
    duration of response, clinical benefit ratio, progressive free-survival, overall survival
Original Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2018)
  • Number of patients experiencing adverse events [ Time Frame: up to 12 months ]
  • Blood plasma concentration of the investigational agent [ Time Frame: up to 20 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Sitravatinib and Nivolumab in Urothelial Carcinoma
Official Title  ICMJE A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients With Advanced or Metastatic Urothelial Carcinoma
Brief Summary The study will evaluate the clinical activity of nivolumab in combination with the investigational agent sitravatinib in patients with advanced or metastatic urothelial carcinoma.
Detailed Description Sitravatinib is an orally-available, small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR family, KIT, FLT3, Trk family, RET, DDR2 and selected Eph family members. Nivolumab is a human IgG monoclonal antibody that binds to the programmed cell death-1(PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response including anti-tumor immune response. Combining an immunotherapeutic PD-L1 checkpoint inhibitor with an agent that has both immune modulatory and antitumor properties could enhance the antitumor efficacy observed with either agent alone. Sitravatinib selectively inhibits key molecular and cellular pathways strongly implicated in checkpoint inhibitor resistance and therefore represents a rational strategy to enhance or restore anti-tumor immunity when combined with nivolumab, a checkpoint inhibitor therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
There are 8 cohorts (having 9-45 maximum patients enrolled in each; based upon response rate and the predicted probability design). Patients are assigned to cohorts based upon their prior treatments for urothelial carcinoma. All patients receive the same treatment.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Urothelial Carcinoma
  • Urothelial Carcinoma Bladder
  • Urothelial Carcinoma Ureter
  • Urothelial Carcinoma of the Renal Pelvis and Ureter
  • Urothelial Carcinoma Urethra
Intervention  ICMJE
  • Drug: Sitravatinib
    Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
    Other Name: MGCD516
  • Drug: Nivolumab
    Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
    Other Name: Opdivo
Study Arms  ICMJE
  • Experimental: Cohort 1
    Patients previously treated with checkpoint inhibitor and platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
    Interventions:
    • Drug: Sitravatinib
    • Drug: Nivolumab
  • Experimental: Cohort 2
    Patients previously treated with checkpoint inhibitor, but ineligible for platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
    Interventions:
    • Drug: Sitravatinib
    • Drug: Nivolumab
  • Experimental: Cohort 3
    Patients previously treated with selected immunotherapies and platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
    Interventions:
    • Drug: Sitravatinib
    • Drug: Nivolumab
  • Experimental: Cohort 4
    Patients previously treated with with selected immunotherapies, but ineligible for platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
    Interventions:
    • Drug: Sitravatinib
    • Drug: Nivolumab
  • Experimental: Cohort 5
    Patients previously treated with platinum-based chemotherapy, but never treated with checkpoint inhibitor. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
    Interventions:
    • Drug: Sitravatinib
    • Drug: Nivolumab
  • Experimental: Cohort 6
    Patients ineligible for treatment with platinum-based chemotherapy and never treated with checkpoint inhibitor. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
    Interventions:
    • Drug: Sitravatinib
    • Drug: Nivolumab
  • Experimental: Cohort 7
    Patients previously treated with antibody-drug conjugate, checkpoint inhibitor and platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
    Interventions:
    • Drug: Sitravatinib
    • Drug: Nivolumab
  • Experimental: Cohort 8
    Patients previously treated with antibody-drug conjugate and checkpoint inhibitor, but ineligible for platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
    Interventions:
    • Drug: Sitravatinib
    • Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 20, 2019)
330
Original Estimated Enrollment  ICMJE
 (submitted: July 20, 2018)
80
Estimated Study Completion Date  ICMJE September 30, 2021
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mirati Therapeutics Study Locator Services 1-844-893-5530 (toll free) miratistudylocator@emergingmed.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03606174
Other Study ID Numbers  ICMJE 516-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mirati Therapeutics Inc.
Study Sponsor  ICMJE Mirati Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Hirak Der-Torossian, MD Mirati Therapeutics Inc.
PRS Account Mirati Therapeutics Inc.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP