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Metastatic Renal Cell CarcinomaPhase 1NCT06132945

A Study of Cabozantinib and Nivolumab With Radiation Therapy for People With Renal Cell Carcinoma That Has Spread to the Brain

A Phase 1 study testing Cabozantinib, Nivolumab and Stereotactic Radiosurgery (SRS) in people with Metastatic Renal Cell Carcinoma and Brain Metastases, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to find out whether the combination of cabozantinib, nivolumab, and radiation therapy is a safe and effective treatment that causes few or mild side effects in people with renal cell cancer that has spread to the brain. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cabozantinib, Nivolumab and Stereotactic Radiosurgery (SRS)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
7 sitesUnited States
Study dates
10 Nov 2023to Nov 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Unresectable advanced or metastatic clear cell or non-clear cell RCC; all histologies acceptable except for chromophobe RCC
  • Brain metastases present, meeting the following criteria:
  • At least 1 brain metastasis measuring ≥0.5cm in any dimension (intracranial RANO-BM measurable disease required)
  • SRS is indicated per treating radiation oncologist
  • Surgical intervention for brain metastases is not planned
  • Able to undergo MRI Brain assessments for radiation planning.
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  • Availability of archival tissue that enables the definitive diagnosis of RCC, accompanied by an associated pathology report. If archival tissue cannot be obtained, PI to provide documented confirmation patient can still enroll onto the study. Specimens can be collected by surgical resection or biopsy of the primary tumor or biopsy or resection of a metastatic lesion.
  • Age ≥18 years
  • KPS ≥ 80
  • Adequate hematologic and end organ function, defined by the following laboratory results obtained within 28 days prior to the first study treatment:
  • ANC ≥ 1500 cells/μL (without granulocyte colony stimulating factor support within 4 weeks prior to Cycle 1, Day 1)
  • WBC counts ≥ 2500/μL
  • Absolute lymphocyte count ≥ 500/μL
  • Platelet count ≥100,000/μL (without transfusion within 4 weeks prior to Cycle 1, Day 1)
  • Hemoglobin ≥9.0 g/dL o Patients may be transfused or receive erythropoietic treatment to meet this criterion.
  • AST, ALT, and alkaline phosphatase ≤ 2.5 x ULN, with the following exceptions:
  • Patients with documented liver metastases: AST and/or ALT ≤ 5 x ULN
  • Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN
  • Serum bilirubin ≤ 1.5 x ULN
  • Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be- enrolled.
  • INR and aPTT ≤ 1.5 x ULN
  • This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
  • Creatinine ≤ 1.5 x ULN or Calculated Creatinine clearance ≥ 30mL/min by institutional standard measurement
  • For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use two adequate methods of contraception, including at least one method with a failure rate of ≥ 1% per year
  • If any Grade ≥1 toxicities occurred in relation to prior treatment, patients must have recovered to baseline or ≤ Grade 1 unless adverse events are clinically insignificant or stable on supportive medication if needed.

Who cannot join

  • Prior treatment with cabozantinib for RCC
  • Receipt of any small molecule kinase inhibitor (including investigational) or VEGFtargeted therapy within 2 weeks before the first dose of study treatment
  • o 2-week washout period was selected in order to facilitate rapid enrollment and treatment of patients given the target population with active brain metastases.
  • Patients requiring whole brain radiotherapy (WBRT).
  • Any prior brain radiotherapy within 28 days prior to enrollment
  • Incomplete healing from prior radiotherapy as determined by the treating radiation oncologist or treating investigator
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  • Diagnosis of autoimmune condition that may worsen during immune checkpoint blockade, with the following exceptions:
  • o Diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
  • Any active or suspected autoimmune disease requiring systemic steroids > 10 mg daily prednisone (or equivalent) or other immunosuppression, except for:
  • those not expected to reoccur
  • Chronic physiologic replacement of ≤10mg prednisone (or equivalent) for treatment of adrenal insufficiency
  • Steroids required for pre-medication reactions
  • Local steroid use is permitted (e.g. intranasal, topical, inhaled, or local steroid injection, i.e. intra-articular)
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Uncontrolled hypercalcemia (≥ 1.5 mmol/L ionized calcium or Ca ≥ 12 mg/dL or corrected serum calcium ≥ ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
  • Participation in an experimental drug study within 28 days of study enrollment
  • Pregnant and lactating women
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, unstable angina, or EF < 50%
  • o Patients with known coronary artery disease, congestive heart failure not meeting the above criteria must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
  • Uncontrolled hypertension (>140 mm Hg systolic or >90 mm Hg diastolic) despite optimal antihypertensive treatment
  • QTcF > 500 msec within 28 days before the first dose of study treatment
  • Major surgical procedure within 14 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
  • o Patients must have completed wound healing from major or minor surgery before first dose of study treatment
  • History of stroke or transient ischemic attack within 6 months prior to Cycle 1, Day 1
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • o Clinically significant hematuria, hematemesis, or hemoptysis of >0.5 tsp (2.5ml) of red blood or other history of significant bleeding within 12 weeks before first dose of study treatment.
  • Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
  • Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
  • Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
  • Concomitant anticoagulation with coumarin agents, direct thrombin inhibitors, factor Xa inhibitor betrixaban, or platelet inhibitors. Other anticoagulants are allowed.
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.
  • o Complete healing of intra-abdominal abscess must be confirmed before the first dose of study treatment
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation
  • Lesions invading or encasing major blood vessels
  • Uncompensated or symptomatic hypothyroidism
  • History of solid organ or allogeneic stem cell transplant
  • Clinically significant active infection including HIV, Hepatitis B, Hepatitis C, acute COVID-19 infection, or other
  • For patients with HIV infection, clinically significant/exclusionary features include: detectable viral load, CD4+ T cell count <300 cells/microL, or history of opportunistic infection
  • For patients with HBV infection, clinically significant/exclusionary features include: HBV surface antigen positivity, detectable HBV DNA by polymerase chain reaction (PCR). Patients with prior HBV infection (HBV core Ab positive, HBV DNA undetectable by PCR, HBV surface antigen negative) are eligible for the study if they are already stable on entecavir or tenofovir
  • Inability to swallow tablets
  • Previously identified allergy or hypersensitivity to components of the treatment
  • Malignancy that requires anti-cancer directed therapy within the last 3 years. Exceptions include those cancers that are considered cured by local therapy (e.g. Basal cell carcinoma, squamous cell carcinoma, ductal carcinoma in situ of breast, bladder, or cervix) or other cancers that have low malignant potential and do not require systemic therapy (e.g. Gleason grade <6 prostate adenocarcinoma)
  • Patients in whom nivolumab treatment is not otherwise feasible (for example, for financial reasons)

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Cancer Suffolk - Commack (All Protocol Activities)

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (All Protocol Activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (All Protocol Activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (All Protocol Activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau (All Protocol Activities)

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: Phase 1b Study of the Safety of Concurrent Cabozantinib and Nivolumab With Radiation Therapy for Brain Metastases in Patients With Metastatic Renal Cell Carcinoma

The purpose of this study is to find out whether the combination of cabozantinib, nivolumab, and radiation therapy is a safe and effective treatment that causes few or mild side effects in people with renal cell cancer that has spread to the brain. The researches will also look at how the study treatment affects the quality of life of participants. They will measure the quality of life by having participants complete questionnaires.

Being tested
Cabozantinib, Nivolumab, Stereotactic Radiosurgery (SRS)
Keywords
Cabozantinib, Nivolumab, Stereotactic Radiosurgery (SRS), 23-138
Medical subject headings
Carcinoma, Renal Cell, Brain Neoplasms

What participants receive

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

  • CabozantinibDrug

    Cabozantinib (40 mg PO daily)

  • NivolumabDevice

    Nivolumab (480 mg IV Day 1)

  • Stereotactic Radiosurgery (SRS)Radiation

    Radiation will be stereotactic radiosurgery, delivered over 1-5 fractions with a total dose of 18-30Gy depending on fractionation schedule per the discretion of the treating radiation oncologist.

Study groups in NCT06132945
Study groupRoleWhat they receive
Cabozantinib and Nivolumab With Radiation TherapyExperimentalPatients being newly initiated on cabo/nivo will be started on with cabozantinib 40 mg PO daily and nivolumab 480 mg IV day Q4 weeks o Dose de-escalation of cabozantinib for toxicity will be allowed per prespecified toxicity dose levels Radiation will be stereotactic radiosurgery, delivered over 1-5 fractions with a total dose of 18-30Gy depending on fractionation schedule per the discretion of the treating radiation oncologist. Standard institutional regimens such as 18-24 Gy in a single fraction, 24-27 Gy in three fractions, and 25-30 Gy in five fractions are permissible.
Receives: Drug: Cabozantinib; Device: Nivolumab; Radiation: Stereotactic Radiosurgery (SRS)

What is being measured

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

  1. percent of enrolled patients who are able to tolerate treatment

    56-day safety monitoring period without unacceptable CNS toxicity. Unacceptable CNS toxicity is defined as any grade ≥3 treatment-emergent neurological disorder, per NCI CTCAE version 5.0 criteria

    Measured: 56-day

Secondary outcomes (2)

  1. rate of CNS adverse events

    CNS adverse events will be reported as a proportion of patients who experience a CNS adverse event of any grade based on CTCAE 5.0

    Measured: 1 year

  2. objective response rate (ORR)

    as measured by RANO-BM criteria

    Measured: 1 year

Timeline

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

  1. First posted15 Nov 2023
  2. Study start10 Nov 2023
  3. Primary completionNov 2027 (estimated)
  4. Study completionNov 2027 (estimated)

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a single-institution, single cohort, phase 1b trial of cabozantinib in combination with nivolumab in patients with metastatic RCC who are planning to undergo radiation therapy for brain metastases.
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06132945
Sponsor's protocol ID
23-138
Status last verified
Nov 2025
First submitted
10 Nov 2023
Last updated
14 Nov 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cabozantinib, Nivolumab and Stereotactic Radiosurgery (SRS) in people with Metastatic Renal Cell Carcinoma and Brain Metastases, run by Memorial Sloan Kettering Cancer Center at 7 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 25 inclusion and 45 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: under way, not looking for participants, as of the sponsor's last update on 14 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

percent of enrolled patients who are able to tolerate treatment (time frame: 56-day). 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 NCT06132945.

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 14 Nov 2025.

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