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Completed

NCT Number: NCT03680521

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

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.

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Key information

Conditions

Clear Cell Renal Cell Carcinoma Adenocarcinoma Carcinoma Carcinoma, Renal Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Sitravatinib

Drug

Sitravatinib oral capsule administered daily for 6-8 weeks in segments 1 and 2.

Nivolumab

Drug

Nivolumab administered as 240 mg IV every 2 weeks for 4-6 weeks in segment 2.

Primary outcomes

  1. 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)

    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.

  2. Point in Time Objective Response Prior to Surgery

    Time frame: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

    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 outcomes

  1. 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)

    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.

  2. Blood Plasma Concentrations of Sitravatinib

    Time frame: Day 1 (pre-dose, and 30 minutes and 4 hours post-dose), Day 15 (pre-dose) and Day 43 (pre-dose)

    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.

  3. Time to Surgery

    Time frame: Day 1 up to date of surgery (maximum time to surgery was approximately 13 weeks)

    Time to surgery was defined as the number of calendar days between Day 1 and the planned nephrectomy.

  4. Disease Free Survival (DFS)

    Time frame: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks)

    DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first.

  5. Percentage 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)

    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.

  6. 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)

    Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean MDSCs using immunohistochemistry.

  7. 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)

    Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean Tregs using immunohistochemistry.

  8. 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)

    Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD4+ T-cells using immunohistochemistry.

  9. 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)

    Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD8+ T-cells using immunohistochemistry.

  10. 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)

    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.

  11. Change From Baseline of Selected Cytokines in Peripheral Blood

    Time frame: Baseline to Day 43

    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).

Sponsors and collaborators

Lead sponsor

Mirati Therapeutics Inc.

Industry

Registry information

Official study title

A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients Undergoing Nephrectomy for Locally-Advanced Clear Cell Renal Cell Carcinoma

Important dates

Study start
2018
Primary completion
2020
Study completion
2023
First posted
Sep 21, 2018
Registry last updated
Oct 4, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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