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Clear Cell Renal Cell CarcinomaPhase 2NCT03680521

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

A Phase 2 study testing Sitravatinib and Nivolumab in people with Clear Cell Renal Cell Carcinoma, run by Mirati Therapeutics Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Clear Cell Renal Cell Carcinoma
What is being tested?
Sitravatinib and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
10 Oct 2018to 18 May 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients Undergoing Nephrectomy for Locally-Advanced 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.

Read the 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.

Being tested
Sitravatinib, Nivolumab
Keywords
ccRCC, MGCD516, Antineoplastic Agents, Immunologic factors, nivolumab, Tyrosine Kinase Inhibitor, VEGFR, TAM RTKs, PD-1, PD-L1
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SitravatinibDrug

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

  • NivolumabDrug

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

Study groups in NCT03680521
Study groupRoleWhat they receive
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.
Receives: Drug: Sitravatinib; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

Secondary outcomes (11)

  1. 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.

    Measured: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)

  2. 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.

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

  3. Time to Surgery

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

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

  4. Disease Free Survival (DFS)

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

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

  5. 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.

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

  6. 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.

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

  7. 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.

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

  8. 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.

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

  9. 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.

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

  10. 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.

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

  11. 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).

    Measured: Baseline to Day 43

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2018
  2. Study start10 Oct 2018
  3. Primary completion27 Apr 2020
  4. Study completion18 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03680521
Sponsor's protocol ID
516-002
Status last verified
Sep 2023
First submitted
18 Sep 2018
Last updated
4 Oct 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sitravatinib and Nivolumab in people with Clear Cell Renal Cell Carcinoma, run by Mirati Therapeutics Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03680521.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2023.

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