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Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

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Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Papillary Renal Cell Carcinoma

Chromophil Renal Cell Carcinoma

Chromophobe Renal Cell Carcinoma

Collecting Duct Carcinoma

Antineoplastic Agents

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Nivolumab

Isotretinoin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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%.

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%.

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

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

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.

cabozantinib

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.

nivolumab

Darren Feldman, MD

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.

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.

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

A Phase 2 Open-Label Study of Nivolumab Combined With Cabozantinib in Subjects With Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma (CA209-9KU)

Memorial Sloan Kettering Cancer Center

Ipilimumab

Eligible patients will be enrolled and receive treatment with

* Cycle 1-4 (cycles of 21 days)

  * Cabozantinib predetermined protocol dosage po daily
  * Nivolumab predetermined protocol dosage via IV every 3 weeks
  * Ipilimumab predetermined protocol dosage via IV every 3 weeks
* After the first four cycles of therapy,

  * Cabozantinib determined protocol dosage po daily
  * Nivolumab predetermined protocol dosage via IV every 3 weeks (cycles of 28 days)

Cabozantinib predetermined protocol dosage po daily

Cabozantinib

Nivolumab predetermined protocol dosage via IV every 3 weeks

Ipilimumab predetermined protocol dosage via IV every 3 weeks

Bradley McGregor, MD

David F McDermott, MD

Hans Hammers, M.D., PhD

This research study will assess whether cabozantinib, nivolumab and ipilimumab in combination are safe and effective in slowing down the growth of kidney cancer(renal cell carcinoma or RCC) that has advanced or spread to other areas the body.

This research study involves an investigational drug combination not approved by the FDA (the U.S. Food and Drug Administration) for your kidney cancer.

The names of the study drugs in this investigational combination are:

* Cabozantinib
* Nivolumab
* Ipilimumab

The research study procedures include screening for eligibility, study treatment, participant evaluations and safety follow-up visits, in addition to general health status follow-up after study treatment.

It is expected that about 40 people will take part in this research study.

Cabozantinib In Combo With NIVO + IPI In Advanced NCCRCC

A Phase 2 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Advanced Non-Clear Cell Renal Cell Carcinoma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Percent of patients who achieve overall response (CR or PR) by RECIST 1.1 will be summarized with 80% two-sided exact binomial confidence intervals (CI)

will be estimated using the method of Kaplan-Meier, for all patients and by histology subtypes. M

the method of Kaplan-Meier, for all patients and by histology subtypes evaluation.

the method of Kaplan-Meier, for all patients and by histology subtypes

For toxicity reporting, all adverse events will be graded and analyzed using CTCAE version 5.

The Functional Assessment of Cancer Therapy-Kidney Symptom (FKSI-19) is a 19 item questionnaire with each item scored on a scale of 0-4 for a total score of 0-76 with higher scores indicating fewer symptom

The Brief Fatigue Inventory (BFI) is a 9-item questionnaire with each item scored on a scale of 0-10.

Scores are categorized as mild (1-3), moderate (4-6), or severe (7-10). A global fatigue score can be found by averaging the score obtained on each test item completed

ORR by RECIST 1.1 according to histology subtypes (Papillary RCC versus other histology types) will be summarized with 80% two-sided exact CIs.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Nivolumab In Combination With Cabozantinib in Patients With Non-Clear Cell Renal Cell Carcinoma	NCT03635892	Advanced or Met... Unclassified Re... Papillary Renal... Fumarate Hydrat... Succinate Dehyd... Collecting Duct... Chromophobe Ren...	cabozantinib nivolumab	18 Years -	Memorial Sloan Kettering Cancer Center
Cabozantinib In Combo With NIVO + IPI In Advanced NCCRCC	NCT04413123	Papillary Renal... Unclassified Re... Translocation R... Chromophobe Ren... Collecting Duct... Renal Cell Carc... Unresectable Ad... Metastatic Ncc ...	Cabozantinib Nivolumab Ipilimumab	18 Years -	Dana-Farber Cancer Institute
Cabozantinib In Combo With NIVO + IPI In Advanced NCCRCC	NCT04413123	Papillary Renal... Unclassified Re... Translocation R... Chromophobe Ren... Collecting Duct... Renal Cell Carc... Unresectable Ad... Metastatic Ncc ...	Cabozantinib Nivolumab Ipilimumab	18 Years -	Dana-Farber Cancer Institute
A Study of Nivolumab In Combination With Cabozantinib in Patients With Non-Clear Cell Renal Cell Carcinoma	NCT03635892	Advanced or Met... Unclassified Re... Papillary Renal... Fumarate Hydrat... Succinate Dehyd... Collecting Duct... Chromophobe Ren...	cabozantinib nivolumab	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for collecting duct renal cell carcinoma