Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Lenvatinib

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Phase 1 study to investigate the tolerability and safety of lenvatinib in combination with Everolimus in participants with unresectable advanced or metastatic RCC.

Study of Lenvatinib in Combination With Everolimus in Participants With Unresectable Advanced or Metastatic Renal Cell Carcinoma (RCC)

Phase 1 Study of Lenvatinib in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic RCC

DLT was defined as toxicity related to the combination therapy and was graded according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03).

BOR included complete response (CR), partial response (PR), stable disease (SD), and PD (progressive disease). BOR was assessed using Response Evaluation Criteria in Solid Tumor (RECIST) 1.1

ORR was defined as the percentage of participants who achieved BOR of CR or PR. ORR was assessed using RECIST 1.1.

DCR was defined as the percentage of participants who achieved BOR of CR, PR, or SD. DCR was assessed based on RECIST 1.1.

Eisai Co., Ltd.

Participants received lenvatinib 18 mg capsules along with everolimus 5 mg tablets, orally, once daily in 28-days treatment cycles up to disease progression, development of unacceptable toxicity, participant's request to discontinue withdrawal of consent, or study termination by sponsor (up to 23 cycles).

Lenvatinib 18 mg + Everolimus 5 mg

Participants received lenvatinib 18 mg capsules along with everolimus 5 mg tablets, orally, once daily in 28-days treatment cycles up to disease progression, development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or study termination by sponsor (up to 23 cycles).

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The safety analysis set was the group of participants who received at least 1 dose of lenvatinib.

Eisai Medical Services

The DLT analysis set was the group of participants who had completed treatment Cycle 1 without major protocol deviation with a treatment compliance of at least 75 percent (%) and had been assessed for DLT, and participants who had experienced DLT during Cycle 1.

Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT)

TEAE

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Lenvatinib: Cycle 1 Day 1

Everolimus: Cycle 1 Day 1

The pharmacokinetic (PK) analysis was group of participants who received at least 1 dose of lenvatinib and had sufficient data from which at least one PK parameter could be calculated.

Cmax: Maximum Observed Plasma Concentration for Levatinib and Everolimus

Lenvatinib: Cycle 1 Day 15

Everolimus: Cycle 1 Day 15

The PK analysis was group of participants who received at least 1 dose of lenvatinib and had sufficient data from which at least one PK parameter could be calculated. The PK analysis set where data at specified time points was available.

Css,Max: Maximum Observed Plasma Concentration at Steady State for Levatinib and Everolimus

The PK analysis was group of participants who received at least 1 dose of lenvatinib and had sufficient data from which at least one PK parameter could be calculated.

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Levatinib and Everolimus

Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State for Levatinib and Everolimus

The PK analysis set was group of participants who received at least 1 dose of lenvatinib and had sufficient data from which at least one PK parameter could be calculated. The PK analysis set where data at specified time points was available.

AUC 0-t: Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration for Levatinib and Everolimus

The efficacy analysis set was the group of participants who received at least 1 dose of lenvatinib.

Number of Participants With Best Overall Response (BOR)

Objective Response Rate (ORR)

Disease Control Rate (DCR)

Less than or equal to (<=) -30%

Greater than (>) -30% to less than (<) 20%

Greater than or equal to (>=) 20%

Number of Participants With the Minimum Percent Change From Baseline in the Sum of Diameters of Target Lesions

Participants received lenvatinib 18 milligram (mg) capsules along with everolimus 5 mg tablets, orally, once daily in 28-days treatment cycles up to disease progression, development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or study termination by sponsor (up to 23 cycles).

Overall Study

Papillary Renal Cell Carcinoma

Chromophil Renal Cell Carcinoma

Chromophobe Renal Cell Carcinoma

Collecting Duct Carcinoma

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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
Study of Lenvatinib in Combination With Everolimus in Participants With Unresectable Advanced or Metastatic Renal Cell Carcinoma (RCC)	NCT02454478	Carcinoma, Rena...	Lenvatinib Everolimus	20 Years -	Eisai Inc.
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

Spots Global Cancer Trial Database for unresectable advanced renal cell carcinoma