Back to resultsNeoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma
Primary Purpose
Clear Cell Renal Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sitravatinib
Nivolumab
Sponsored by
About this trial
This is an interventional treatment trial for Clear Cell Renal Cell Carcinoma focused on measuring ccRCC, MGCD516, Antineoplastic Agents, Immunologic factors, nivolumab, Tyrosine Kinase Inhibitor, VEGFR, TAM RTKs, PD-1, PD-L1
Eligibility Criteria
Inclusion Criteria:
- Imaging results consistent with locally-advanced RCC
- Candidate for partial or complete nephrectomy as part of treatment plan.
- Measurable disease per RECIST version 1.1.
- ECOG performance status 0 or 1.
- Adequate bone marrow and organ function.
Exclusion Criteria:
- Prior systemic anti-tumor treatment for RCC.
- Patients who are receiving any other investigational agents.
- 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.
- Inability to undergo baseline tumor biopsy.
- Active or prior documented autoimmune or immunocompromising conditions.
- Uncontrolled hypertension.
Sites / Locations
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sitravatinib and nivolumab
Arm Description
Sitravatinib 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.
Outcomes
Primary Outcome Measures
Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery
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.
Point in Time Objective Response Prior to Surgery
Number and percentage of participants who experienced a response prior to surgery in accordance with 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;
Stable Disease (SD) is concluded when the single point in time response does not qualify for CR, PR or Progressive Disease (PD);
PD is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing nontarget lesions.
Secondary Outcome Measures
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
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.
Blood Plasma Concentrations of Sitravatinib
The blood plasma concentrations of sitravatinib were determined using blood samples. Blood samples for analysis of blood plasma concentrations of sitravatinib were taken after scheduled vital signs and triplicate electrocardiogram assessments.
Time to Surgery
Time to surgery was defined as the number of calendar days between Day 1 and the planned nephrectomy.
Disease Free Survival (DFS)
DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first.
Percentage Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor
Tumor tissue was collected from study biopsies and surgical samples. Tumor tissue was used to assess the mean PD-L1 expression in the tumor via immunohistochemistry and/or immunofluorescence.
Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean MDSCs using immunohistochemistry.
Change From Baseline in Regulatory T-cells (Tregs) in the Tumor
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean Tregs using immunohistochemistry.
Change From Baseline in CD4+ T-cells in the Tumor
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD4+ T-cells using immunohistochemistry.
Change From Baseline in CD8+ T-cells in the Tumor
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD8+ T-cells using immunohistochemistry.
Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean ratio of Type 1 to Type 2 tumor associated macrophages using immunohistochemistry.
Change From Baseline of Selected Cytokines in Peripheral Blood
Cytokines measured in peripheral blood were soluble CD27 (sCD27), eotaxin, macrophage inflammatory protein 1b (MIP-1b), and soluble programmed cell death protein 1 (sPD-1).
Full Information
NCT ID
NCT03680521
First Posted
September 18, 2018
Last Updated
September 11, 2023
Sponsor
Mirati Therapeutics Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03680521
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
October 10, 2018 (Actual)
Primary Completion Date
April 27, 2020 (Actual)
Study Completion Date
May 18, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirati Therapeutics Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clear Cell Renal Cell Carcinoma
Keywords
ccRCC, MGCD516, Antineoplastic Agents, Immunologic factors, nivolumab, Tyrosine Kinase Inhibitor, VEGFR, TAM RTKs, PD-1, PD-L1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sitravatinib and nivolumab
Arm Type
Experimental
Arm Description
Sitravatinib 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.
Intervention Type
Drug
Intervention Name(s)
Sitravatinib
Intervention Description
Sitravatinib oral capsule administered daily for 6-8 weeks in segments 1 and 2.
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Intervention Description
Nivolumab administered as 240 mg IV every 2 weeks for 4-6 weeks in segment 2.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery
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.
Time Frame
Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Title
Point in Time Objective Response Prior to Surgery
Description
Number and percentage of participants who experienced a response prior to surgery in accordance with 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;
Stable Disease (SD) is concluded when the single point in time response does not qualify for CR, PR or Progressive Disease (PD);
PD is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing nontarget lesions.
Time Frame
Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Secondary Outcome Measure Information:
Title
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
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.
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)
Title
Blood Plasma Concentrations of Sitravatinib
Description
The blood plasma concentrations of sitravatinib were determined using blood samples. Blood samples for analysis of blood plasma concentrations of sitravatinib were taken after scheduled vital signs and triplicate electrocardiogram assessments.
Time Frame
Day 1 (pre-dose, and 30 minutes and 4 hours post-dose), Day 15 (pre-dose) and Day 43 (pre-dose)
Title
Time to Surgery
Description
Time to surgery was defined as the number of calendar days between Day 1 and the planned nephrectomy.
Time Frame
Day 1 up to date of surgery (maximum time to surgery was approximately 13 weeks)
Title
Disease Free Survival (DFS)
Description
DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first.
Time Frame
Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks)
Title
Percentage Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor
Description
Tumor tissue was collected from study biopsies and surgical samples. Tumor tissue was used to assess the mean PD-L1 expression in the tumor via immunohistochemistry and/or immunofluorescence.
Time Frame
Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Title
Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor
Description
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean MDSCs using immunohistochemistry.
Time Frame
Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Title
Change From Baseline in Regulatory T-cells (Tregs) in the Tumor
Description
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean Tregs using immunohistochemistry.
Time Frame
Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Title
Change From Baseline in CD4+ T-cells in the Tumor
Description
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD4+ T-cells using immunohistochemistry.
Time Frame
Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Title
Change From Baseline in CD8+ T-cells in the Tumor
Description
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD8+ T-cells using immunohistochemistry.
Time Frame
Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Title
Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor
Description
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean ratio of Type 1 to Type 2 tumor associated macrophages using immunohistochemistry.
Time Frame
Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Title
Change From Baseline of Selected Cytokines in Peripheral Blood
Description
Cytokines measured in peripheral blood were soluble CD27 (sCD27), eotaxin, macrophage inflammatory protein 1b (MIP-1b), and soluble programmed cell death protein 1 (sPD-1).
Time Frame
Baseline to Day 43
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Imaging results consistent with locally-advanced RCC
Candidate for partial or complete nephrectomy as part of treatment plan.
Measurable disease per RECIST version 1.1.
ECOG performance status 0 or 1.
Adequate bone marrow and organ function.
Exclusion Criteria:
Prior systemic anti-tumor treatment for RCC.
Patients who are receiving any other investigational agents.
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.
Inability to undergo baseline tumor biopsy.
Active or prior documented autoimmune or immunocompromising conditions.
Uncontrolled hypertension.
Facility Information:
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma
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