Clinical trial NCT03680521: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clear Cell Renal Cell Carcinoma
Keywords: ccRCC
MGCD516
Antineoplastic Agents
Immunologic factors
nivolumab
Tyrosine Kinase Inhibitor
VEGFR
TAM RTKs
PD-1
PD-L1
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2018-09-21
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery
timeFrame: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
measure: Point in Time Objective Response Prior to Surgery
timeFrame: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Secondary outcomes:
measure: Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)
measure: Blood Plasma Concentrations of Sitravatinib
timeFrame: Day 1 (pre-dose, and 30 minutes and 4 hours post-dose), Day 15 (pre-dose) and Day 43 (pre-dose)
measure: Time to Surgery
timeFrame: Day 1 up to date of surgery (maximum time to surgery was approximately 13 weeks)
measure: Disease Free Survival (DFS)
timeFrame: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks)
measure: Percentage Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor
timeFrame: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
measure: Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor
timeFrame: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
measure: Change From Baseline in Regulatory T-cells (Tregs) in the Tumor
timeFrame: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
measure: Change From Baseline in CD4+ T-cells in the Tumor
timeFrame: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
measure: Change From Baseline in CD8+ T-cells in the Tumor
timeFrame: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
measure: Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor
timeFrame: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
measure: Change From Baseline of Selected Cytokines in Peripheral Blood
timeFrame: Baseline to Day 43
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
References: