Phase 1b Study of the Safety of Concurrent Cabozantinib and Nivolumab With Radiation Therapy for Brain Metastases in Patients With Metastatic Renal Cell Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Cabozantinib
- Conditions
- Metastatic Renal Cell Carcinoma
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 2
- Locations
- 7
- Primary Endpoint
- percent of enrolled patients who are able to tolerate treatment
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •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)
Exclusion Criteria
- •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
Arms & Interventions
Cabozantinib and Nivolumab With Radiation Therapy
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.
Intervention: Cabozantinib
Cabozantinib and Nivolumab With Radiation Therapy
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.
Intervention: Nivolumab
Cabozantinib and Nivolumab With Radiation Therapy
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.
Intervention: Stereotactic Radiosurgery (SRS)
Outcomes
Primary Outcomes
percent of enrolled patients who are able to tolerate treatment
Time Frame: 56-day
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
Secondary Outcomes
- rate of CNS adverse events(1 year)
- objective response rate (ORR)(1 year)