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

NCT06132945 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 23-138
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 7

Brief 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. 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.

Conditions

Metastatic Renal Cell Carcinoma; Brain Metastases

Keywords

Cabozantinib; Nivolumab; Stereotactic Radiosurgery (SRS); 23-138

Outcome Measures

Primary Outcomes (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

  56-day

Secondary Outcomes (2)

• rate of CNS adverse events

  1 year

• objective response rate (ORR)

  1 year

Study Arms (1)

Cabozantinib and Nivolumab With Radiation Therapy

EXPERIMENTAL

Patients 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.

Drug: Cabozantinib; Device: Nivolumab; Radiation: Stereotactic Radiosurgery (SRS)

Interventions

Cabozantinib DRUG

Cabozantinib (40 mg PO daily)

Cabozantinib and Nivolumab With Radiation Therapy

Nivolumab DEVICE

Nivolumab (480 mg IV Day 1)

Cabozantinib and Nivolumab With Radiation Therapy

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.

Cabozantinib and Nivolumab With Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Exelixis: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

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

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Renal Cell; Brain Neoplasms

Interventions

cabozantinib; Radiosurgery

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Ritesh Kotecha, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 10, 2023
• First Posted: November 15, 2023
• Study Start: November 10, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (7)