Clinical Trials /

Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma

NCT03680521

Description:

The study will evaluate the clinical activity of sitravatinib in combination with nivolumab in patients with locally-advanced clear cell renal cell carcinoma (ccRCC) in the neoadjuvant setting prior to nephrectomy.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT03680521

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma
  • Official Title: A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients Undergoing Nephrectomy for Locally-Advanced Clear Cell Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 516-002
  • NCT ID: NCT03680521

Conditions

  • Clear Cell Renal Cell Carcinoma

Interventions

DrugSynonymsArms
SitravatinibSitravatinib and nivolumab
NivolumabSitravatinib and nivolumab

Purpose

The study will evaluate the clinical activity of sitravatinib in combination with nivolumab in patients with locally-advanced clear cell renal cell carcinoma (ccRCC) in the neoadjuvant setting prior to nephrectomy.

Detailed Description

      Sitravatinib is a receptor tyrosine kinase inhibitor (TKI) that targets multiple closely
      related receptor tyrosine kinase pathways including VEGFR, PDGFR, c-KIT, MET, and the TAM
      family of receptors (TYRO3, AXL, and MER). Nivolumab is a monoclonal antibody directed
      against PD-1 and blocks the interaction between PD-1 and its ligands, thereby releasing
      PD-1-mediated inhibition of T-cell proliferation (including cytotoxic CD8+ T-cells) and
      cytokine production. Together, sitravatinib and nivolumab may cooperate to elicit greater
      anti-tumor activity than either agent alone, as sitravatinib is predicted to enhance several
      steps in the cancer immunity cycle that may augment the efficacy of nivolumab.

Trial Arms

NameTypeDescriptionInterventions
Sitravatinib and nivolumabExperimentalSitravatinib oral capsule administered daily 2 weeks alone then in combination with nivolumab administered as 240 mg IV every 2 weeks. Total treatment duration: 6-8 weeks prior to planned nephrectomy.
  • Sitravatinib
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          1. Imaging results consistent with locally-advanced RCC

          2. Candidate for partial or complete nephrectomy as part of treatment plan.

          3. Measurable disease per RECIST version 1.1.

          4. ECOG performance status 0 or 1.

          5. Adequate bone marrow and organ function.

        Exclusion Criteria:

          1. Prior systemic anti-tumor treatment for RCC.

          2. Patients who are receiving any other investigational agents.

          3. Clinical status indicating that immediate surgery (within 6 weeks) is warranted
             regardless of whether neoadjuvant therapy is to be administered, as assessed by the
             treating surgeon.

          4. Inability to undergo baseline tumor biopsy.

          5. Active or prior documented autoimmune or immunocompromising conditions.

          6. Uncontrolled hypertension.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery
Time Frame:Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Safety Issue:
Description:Objective response is defined as the percent of participants documented by investigator assessment to have Complete Response (CR) or Partial Response (PR) in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; PR is defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions.

Secondary Outcome Measures

Measure:Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Time Frame:Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)
Safety Issue:
Description:TEAEs occured after the first dose of any study treatment or any preexisting condition that increased in severity after the first dose of study treatment and prior to 28 days after last dose of study drug or surgery, whichever occurred last. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measure:Blood Plasma Concentrations of Sitravatinib
Time Frame:Day 1 (pre-dose, and 30 minutes to 4 hours post-dose), Day 15 (pre-dose) and Day 43 (pre-dose)
Safety Issue:
Description:
Measure:Time to Surgery
Time Frame:Day 1 up to date of surgery (maximum time to surgery was approximately 13 weeks)
Safety Issue:
Description:Time to surgery was defined as the number of calendar days between Day 1 and the planned nephrectomy.
Measure:Disease Free Survival (DFS)
Time Frame:Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks)
Safety Issue:
Description:DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first.
Measure:Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor
Time Frame:Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Safety Issue:
Description:
Measure:Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor
Time Frame:Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Safety Issue:
Description:
Measure:Change From Baseline in Regulatory T-cells (Tregs) in the Tumor
Time Frame:Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Safety Issue:
Description:
Measure:Change From Baseline in CD4+ T-cells in the Tumor
Time Frame:Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Safety Issue:
Description:
Measure:Change From Baseline in CD8+ T-cells in the Tumor
Time Frame:Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Safety Issue:
Description:
Measure:Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor
Time Frame:Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Safety Issue:
Description:
Measure:Change From Baseline of Selected Cytokines in Peripheral Blood
Time Frame:Baseline to Day 43
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Mirati Therapeutics Inc.

Trial Keywords

  • ccRCC
  • MGCD516
  • Antineoplastic Agents
  • Immunologic factors
  • nivolumab
  • Tyrosine Kinase Inhibitor
  • VEGFR
  • TAM RTKs
  • PD-1
  • PD-L1

Last Updated

May 19, 2021