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Advanced Clear Cell Renal Cell CarcinomaPhase 2NCT04904302

Sitravatinib and Nivolumab for the Treatment of Metastatic or Advanced Clear Cell Renal Cell Cancer

A Phase 2 study testing Nivolumab, Quality-of-Life Assessment and Questionnaire Administration in people with Advanced Clear Cell Renal Cell Carcinoma and Metastatic Clear Cell Renal Cell Carcinoma, run by M.D. Anderson Cancer Center at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial investigates the effect of sitravatinib and nivolumab in treating patients with clear cell renal cell cancer that has spread to other places in the body (metastatic/advanced). Sitravatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab, Quality-of-Life Assessment and Questionnaire Administration
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesUnited States
Study dates
3 May 2022to 11 Mar 2026
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Patients with histologically or cytologically confirmed metastatic/advanced clear cell RCC, or RCC with a clear cell component, who have received 1 or 2 prior lines of treatment in the advanced or metastatic setting, and the most recent treatment must include a PD-1 or PD-L1 CPI, cabozantinib, or lenvatinib. Examples of acceptable prior regimens include: nivolumab plus ipilimumab (cohort A), pembrolizumab plus axitinib, avelumab plus axitinib, or VEGF-targeted monotherapy followed by nivolumab monotherapy (cohort B), or cabozantinib or lenvatinib with or without everolimus, received alone sequentially before PD-1/PD-L1 inhibitors, or in combination with CPIs (cohort C)
  • There must be evidence of progression on or after treatment (at any point after completing prior therapy) with a PD-1/PD-L1-containing regimen as the last treatment received within 6 months of enrollment
  • Patients must have at least one measurable site of disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures >= 15 mm with conventional techniques or >= 10 mm with more sensitive techniques such as magnetic resonance imaging (MRI) or spiral computed tomography (CT) scan. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
  • Karnofsky performance status >= 70
  • Age >= 18 years
  • Hemoglobin >= 9 g/dl (treatment allowed)
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  • May receive transfusion
  • Absolute neutrophil count >= 1,000/uL
  • Platelets >= 75,000/uL
  • Total bilirubin =< 1.5 mg/dL
  • For patients with Gilbert's disease, total bilirubin should =< 3 mg/dL (=< 51.3 umol/L)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (ULN), except in known hepatic metastasis, wherein may be < 5 x ULN
  • Serum Creatinine =< 1.5 x ULN (as long as patient does not require dialysis)
  • If creatinine is not < 1.5 x ULN, then calculate by Cockcroft-Gault methods or local institutional standard and creatinine clearance (CrCl) must be >= 40 mL/kg/1.73 m^2
  • Institutional normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x ULN prior to study entry. Therapeutic anticoagulation is permitted if: on a stable dose of low molecular weight heparin (LMWH) for > 2 weeks (14 days) at the time of enrollment or on a direct oral anticoagulant (DOAC) for > 2 weeks at time of enrollment
  • Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) before study entry. Pregnancy test must be repeated if performed > 14 days before starting study drug
  • Women must not be breastfeeding
  • Patients with a history of major psychiatric illness must be judged (by the treating physician) able to fully understand the investigational nature of the study and the risks associated with the therapy
  • Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected or treated with radiosurgery or gamma knife, without recurrence or edema for 1 month (4 weeks)

Who cannot join

  • Patients must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, adequately treated (without recurrence post-resection or post- radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, or active non-threatening second malignancy that would not, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial. Examples include but not limited to: urothelial cancer grade Ta or T1, adenocarcinoma of the prostate treated by active surveillance
  • Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks (14 days) from enrollment into this study (including chemotherapy and targeted therapy) are excluded. Also, patients who have completed palliative radiation therapy more than 14 days prior to the first dose of sitravatinib are eligible
  • Patients who had a major surgery or significant traumatic injury (injury requiring > 28 days to heal) within 28 days of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients that are expected to require major surgery during the course of the study
  • Patients with a prior history of grade 3 or worse immune-related adverse events attributed to CPIs (PD-1, PD-L1, or CTLA-4), except endocrine adverse events with appropriate hormone replacement or asymptomatic amylase/lipase elevations
  • Active or prior documented autoimmune disease, as follows:
  • Inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
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  • Interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
  • Other medically important autoimmune disease within 2 years before first dose of study treatment. Note: Patients with type 1 diabetes, vitiligo, Graves' disease requiring only hormone replacement, residual hypothyroidism requiring only hormone replacement, or psoriasis or Sjogren's syndrome not requiring systemic treatment are permitted
  • Immunocompromising conditions, as follows:
  • Known acute or chronic human immunodeficiency virus (HIV) infection
  • History of primary immunodeficiency
  • History or allogeneic transplant
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of study treatment, with the exception of topical, ocular, intranasal, and inhaled corticosteroids, or systemic corticosteroids at an equivalent dose =< 10 mg of prednisone daily
  • Any underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea, uncontrolled nausea, vomiting, malabsorption syndrome or small bowel resection that may significantly alter the absorption of sitravatinib
  • Patients receiving any concomitant systemic therapy for renal cell cancer are excluded
  • Patients must not be scheduled to receive another experimental drug while on this study
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • Symptomatic congestive heart failure of New York Heart Association class III or IV
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
  • Severely impaired lung function as defined as 02 saturation that is 88% or less at rest on room air
  • Uncontrolled diabetes as defined by blood glucose > 200 mg/dl (11.1 mmol/l)
  • Systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement) despite appropriate antibiotics or other treatment
  • Liver disease, such as cirrhosis or chronic active hepatitis; Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection
  • Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of sitravatinib or nivolumab or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
  • Patients should not receive immunization with attenuated live vaccines within one week (7 days) of study entry or during study period
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If a patient can become pregnant or father a child, appropriate birth control methods, including a double-barrier method (2 methods at the same time), are required while on study and for 23 weeks (females) or 31 weeks (males) after you stop receiving the study drugs. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days prior to study entry. Pregnancy test must be repeated if performed > 14 days before administration of sitravatinib)
  • Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study
  • Concurrent therapy with medications known to significantly prolong the QT interval and/or associated with increased risk for Torsade de Pointes arrhythmia. The principal investigator (PI) is the final arbiter in questions related to eligibility
  • Patients with left ventricular ejection fraction (LVEF) < 40

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University Hospital / IU Simon Cancer Center

    Indianapolis, Indiana, 46202

Other trials in United States

About this study

Official title: A Phase II Trial of Sitravatinib Plus Nivolumab in Patients With Metastatic Clear Cell Renal Cell Carcinoma Who Progressed on Prior Treatment Acronym: SNAPI (Sitravatinib and Nivolumab After Prior Immunotherapy)

This phase II trial investigates the effect of sitravatinib and nivolumab in treating patients with clear cell renal cell cancer that has spread to other places in the body (metastatic/advanced). Sitravatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sitravatinib and nivolumab may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the objective response rate (ORR) and disease control rate (DCR) at 24 weeks of sitravatinib 100 milligrams (mg) by mouth (PO) daily plus nivolumab 480 mg intravenously (IV) every 4 weeks in patients with metastatic renal cell carcinoma (mRCC) who progress on prior PD-1 or PD-L1 immune checkpoint inhibitors (CPIs), cabozantinib, or lenvatinib, as defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

SECONDARY OBJECTIVES:

  1. To estimate the overall survival (OS), progression-free survival (PFS), duration of response (DOR), and 1-year OS of sitravatinib plus nivolumab in the same population.

II. To determine the safety, tolerability, and impact on health-related quality of life of sitravatinib plus nivolumab in patients with mRCC who progress on PD-1/PD-L1 CPIs, cabozantinib, or lenvatinib as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

EXPLORATORY OBJECTIVE:

  1. To assess how the immune landscape, transcriptome, and genome change after contemporary first-line treatment via tumor tissue biopsy obtained at time of enrollment, 4 weeks after treatment with sitravatinib plus nivolumab, and at time of progression, as well as blood sample collection.

OUTLINE:

Patients receive sitravatinib PO once daily (QD) and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Nivolumab, Quality-of-Life Assessment, Questionnaire Administration, Sitravatinib
Medical subject headings
Clear-cell metastatic renal cell carcinoma, Carcinoma, Renal Cell

What participants receive

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

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • SitravatinibDrug

    Also called MGCD516

    Given PO

Study groups in NCT04904302
Study groupRoleWhat they receive
Treatment (sitravatinib, nivolumab)ExperimentalPatients receive sitravatinib PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Sitravatinib

What is being measured

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

  1. Objective response rate

    Will be defined as complete response + partial response. Will be defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

    Measured: At 24 weeks

  2. Disease control rate

    Will be defined by RECIST 1.1.

    Measured: At 24 weeks

Secondary outcomes (5)

  1. Overall survival

    Kaplan-Meier survival curves will be generated. Cox regression models will be fitted to assess the association between prognostic variables, and the survival endpoints.

    Measured: At 1 year

  2. Progression free survival

    Kaplan-Meier survival curves will be generated. Cox regression models will be fitted to assess the association between prognostic variables, and the survival endpoints.

    Measured: At 1 year

  3. Duration of response

    Kaplan-Meier survival curves will be generated. Cox regression models will be fitted to assess the association between prognostic variables, and the survival endpoints.

    Measured: At 1 year

  4. Incidence of adverse events

    Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will be summarized using descriptive statistics (e.g., frequency, 95% confidence interval) by type and grade.

    Measured: Up to 6 years

  5. Health-related quality-of-life (QOL)

    Will be assessed using the Functional Assessment of Cancer Therapy- Kidney Symptom Index- Disease Related Symptoms questionnaire. Descriptive statistics (e.g., means, ranges, standard deviations) will be computed, together with ninety-five percent confidence intervals for the means. Proportions of subjects falling outside normative ranges for the stress and QOL measures will also be calculated. Values for the standardized scales will be compared to normative data and patients receiving other types of cancer therapy. Graphical methods (e.g., boxplots and histograms) will be employed to more closely examine the distributions of the measures at each time point. Change scores for the stress and QOL measures will be computed as the simple differences between the baseline measure and subsequent evaluations. Paired t-tests will be used to evaluate the change of the stress and QOL measures between different time points.

    Measured: Up to 24 weeks

Timeline

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

  1. First posted27 May 2021
  2. Study start3 May 2022
  3. Primary completion11 Mar 2026
  4. Study completion11 Mar 2026

Why it stopped: Withdrawal of funding from the supporter (Mirati Therapeutics)

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
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04904302
Sponsor's protocol ID
2021-0057
Other IDs
NCI-2021-03344, 2021-0057
Status last verified
Mar 2026
First submitted
17 May 2021
Last updated
20 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Hahn AW, Adra N, Vaishampayan U, Xiao L, Dizman N, Yuan Y, Mukhida SS, Campbell MT, Gao J, Zurita AJ, Jonasch E, Tannir NM, Shah AY, Msaouel P. A phase II trial of sitravatinib + nivolumab after progression on immune checkpoint inhibitor in patients with metastatic clear cell RCC. Oncologist. 2025 Apr 4;30(4):oyaf053. doi: 10.1093/oncolo/oyaf053.

    PubMed 40212021

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Quality-of-Life Assessment and Questionnaire Administration in people with Advanced Clear Cell Renal Cell Carcinoma and Metastatic Clear Cell Renal Cell Carcinoma, run by M.D. Anderson Cancer Center at 2 sites 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 19 inclusion and 30 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: stopped early, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

The study was stopped early (reason given: Withdrawal of funding from the supporter (Mirati Therapeutics)). Results are not available in the source record.

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?

Objective response rate (time frame: At 24 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 NCT04904302, which also lists 1 linked publication.

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 20 Mar 2026.

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