A Study of Nivolumab In Combination With Cabozantinib in Patients With Non-Clear Cell Renal Cell Carcinoma

NCT03635892 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 18-254
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to compare any good and bad effects of using a combination of nivolumab (Opdivo®) and cabozantinib (Cabometyx®) in people with metastatic kidney cancer.

Conditions

Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma; Unclassified Renal Cell Carcinoma; Papillary Renal Cell Carcinoma; Fumarate Hydratase Deficient Renal Cell Carcinoma; Succinate Dehydrogenase Deficient Renal Cell Carcinoma; Collecting Duct Renal Cell Carcinoma; Chromophobe Renal Cell Carcinoma

Keywords

Nivolumab; Cabozantinib; 18-254

Outcome Measures

Primary Outcomes (1)

• objective response rate

  per RECIST v1.1

  2 years

Study Arms (4)

Cohort 1: Unclassified, papillary, and HL RCC

EXPERIMENTAL

Cohort 1 is designed as a single stage study with a total sample size of 20. This design discriminates between ORR rates of 10 and 35%.

Drug: cabozantinib; Drug: nivolumab

Cohort 2: Chromophobe RCC

EXPERIMENTAL

Cohort 2 is designed as a Simon's optimal two-stage design with a total possible sample size of 17. This design discriminates between ORR rates of 5 and 25%.

Drug: cabozantinib; Drug: nivolumab

Cohort 3: Unclassified, papillary, and HL RCC

EXPERIMENTAL

Cohort 3 is designed as an expansion cohort of Cohort 1 with 20 additional patients to obtain a more precise estimate of the ORR and clinical outcomes

Drug: cabozantinib; Drug: nivolumab

Cohort 4: Unclassified, papillary, and HL RCC

EXPERIMENTAL

Cohort 4 is an expansion of Cohorts 1+3, which will accure an additional 40 patients

Drug: cabozantinib; Drug: nivolumab

Interventions

cabozantinib DRUG

cabozantinib 40mg, self administered orally once daily on a continuous schedule (days 1-28) Patients will continue to take cabozantinib until disease progression (unless continuing treatment beyond progression), major toxicity, or withdrawal from the study for any reason.

Also known as: CABOMETYX®

Cohort 1: Unclassified, papillary, and HL RCC; Cohort 2: Chromophobe RCC; Cohort 3: Unclassified, papillary, and HL RCC; Cohort 4: Unclassified, papillary, and HL RCC

nivolumab DRUG

Patients will receive an intravenous infusion of nivolumab, per institutional standards, at 240 mg on Cycle 1, Day 1 and will return to the center approximately every two weeks (14 ± 3 days) for subsequent infusions until disease progression (unless continuing treatment beyond progression), major toxicity, or withdrawal from the study for any reason.

Also known as: Opdivo

Cohort 1: Unclassified, papillary, and HL RCC; Cohort 2: Chromophobe RCC; Cohort 3: Unclassified, papillary, and HL RCC; Cohort 4: Unclassified, papillary, and HL RCC

Eligibility Criteria

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

You may qualify if:

• Signed and dated IRB-approved Informed Consent Form
• Pathologic or histologically confirmed unresectable advanced or metastatic nccRCC
• or 1 prior systemic therapies, including treatment in the adjuvant setting
• Availability of a representative formalin fixed, paraffin embedded tumor specimen or fresh frozen tissue specimen that enables the definitive diagnosis of RCC, accompanied by an associated pathology report. Specimens can be collected by surgical resection or biopsy of the primary tumor or biopsy or resection of a metastatic lesion.
• Measurable disease, as defined by RECIST 1.1
• Age ≥18 years
• KPS ≥ 70
• Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless adverse events (AE(s)) are clinically nonsignificant and/or stable on supportive therapy.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
• ANC ≥ 1500 cells/μL (without granulocyte colony stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
• WBC counts ≥ 2500/μL and ≤ 15,000/μL without G-CSF
• Lymphocyte count ≥ 500/μL
• Platelet count ≥100,000/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
• Hemoglobin ≥9.0 g/dL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN if patient has documented bone metastases.

You may not qualify if:

• Prior treatment with an immunotherapy agent including high dose IL-2, anti-CTLA-4, anti-PD1, and anti-PD-L1 agents
• Prior treatment with cabozantinib for non-clear cell RCC
• Receipt of any type of small molecule kinase inhibitor within 2 weeks of treatment.
• Receipt of any type of anti-cancer antibody, cytotoxic anticancer therapy, or any other investigational agents within 4 weeks of treatment start
• Known malignancies of the brain or spinal cord or leptomeningeal disease
• Patients requiring pain medication must be on a stable regimen at study entry
• Systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroids \> 10 mg daily prednisone equivalents are allowed in the absence of autoimmune disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• 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
• Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy
• Pregnant and lactating women History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• History of HIV infection
• Patients with active or chronic hepatitis B or hepatitis C infection
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 6 months, unstable arrhythmias, unstable angina, or EF \< 50%
• Uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Lee CH, Voss MH, Carlo MI, Chen YB, Zucker M, Knezevic A, Lefkowitz RA, Shapnik N, Dadoun C, Reznik E, Shah NJ, Owens CN, McHugh DJ, Aggen DH, Laccetti AL, Kotecha R, Feldman DR, Motzer RJ. Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. J Clin Oncol. 2022 Jul 20;40(21):2333-2341. doi: 10.1200/JCO.21.01944. Epub 2022 Mar 17.

  PMID: 35298296 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

cabozantinib; Nivolumab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Darren Feldman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single institution open-label phase II trial of cabozantinib and nivolumab in patients with advanced or metastatic non-clear cell Renal Cell Carcinoma (nccRCC), who have not received prior PD-1/PD-L1 directed therapy. This study is designed as separate cohorts defined by histology across three cohorts.

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: August 17, 2018
• Study Start: August 13, 2018
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-09

Locations

US (7)