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

Running, not enrolling · Phase 1

Conditions studied: Metastatic Renal Cell Carcinoma, Brain Metastases

In brief

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.

Key facts

Study ID

NCT06132945

Run by

Memorial Sloan Kettering Cancer Center

People needed

2

Starts

2023-11-10

Expected to finish

2027-11-01

Last updated by the study team

2025-11-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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
• a. 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.

You may not qualify if…

• 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
• 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

Where it is running

• Memorial Sloan Kettering Basking Ridge (All Protocol Activities) — Basking Ridge, New Jersey, United States
• Memorial Sloan Kettering Monmouth (All Protocol Activities) — Middletown, New Jersey, United States
• Memorial Sloan Kettering Bergen (All Protocol Activities) — Montvale, New Jersey, United States
• Memorial Sloan Kettering Cancer Suffolk - Commack (All Protocol Activities) — Commack, New York, United States
• Memorial Sloan Kettering Westchester (All Protocol Activities) — Harrison, New York, United States
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States
• Memorial Sloan Kettering Nassau (All Protocol Activities) — Uniondale, New York, United States

Full record on ClinicalTrials.gov

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