Cabozantinib In Combo With NIVO + IPI In Advanced NCCRCC

NCT04413123 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 19-789
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Papillary Renal Cell Carcinoma; Unclassified Renal Cell Carcinoma; Translocation Renal Cell Carcinoma; Chromophobe Renal Cell Carcinoma; Collecting Duct Renal Cell Carcinoma; Renal Cell Carcinoma; Unresectable Advanced Renal Cell Carcinoma; Metastatic Ncc Renal Cell Carcinoma

Keywords

Papillary Renal Cell Carcinoma; Unclassified Renal Cell Carcinoma; Translocation Renal Cell Carcinoma; Chromophobe Renal Cell Carcinoma; Collecting duct Renal Cell Carcinoma; Renal Cell Carcinoma; Unresectable Advanced Renal Cell Carcinoma; Metastatic ncc Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  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)

  tart of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started up to 21 Months

Secondary Outcomes (7)

• Duration of response (DOR)

  first documentation of response, to the earlier of the first documentation of disease progression or death from any cause, and calculated for patients with a best confirmed response of CR up to 21 Months

• Progression-free survival (PFS)

  trial treatment start to the earlier of progression or death due to any cause per investigator assessment. Participants alive without disease progression are censored at date of last disease evaluation up to 21 Months

• Overall survival (OS)

  from trial treatment start to death due to any cause or censored at date last known alive up to 21 Months

• "Number of Participants with TreatmentRelated Adverse Events as Assessed by CTCAE version 5.

  Baseline, day 1 of every cycle (21 days for first 4 cycles and then 28 days for each cycle tehreafter) and End of Treatment up 21 months

• Quality of life- FKSI-19 Scale

  12 weeks for the first assessment, then every 8 weeks (+/- 7 days) for the first 6 months. Then take place every 12 weeks (+/- 7 days)

Study Arms (1)

Cabozantinib

EXPERIMENTAL

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)

Drug: Cabozantinib; Drug: Nivolumab; Drug: Ipilimumab

Interventions

Cabozantinib DRUG

Cabozantinib predetermined protocol dosage po daily

Also known as: COMETRIQ™, CABOMETYX™

Cabozantinib

Nivolumab DRUG

Nivolumab predetermined protocol dosage via IV every 3 weeks

Also known as: Opdivo®

Cabozantinib

Ipilimumab DRUG

Ipilimumab predetermined protocol dosage via IV every 3 weeks

Also known as: Yervoy

Cabozantinib

Eligibility Criteria

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

You may qualify if:

• histologically or cytologically confirmed unresectable advanced or metastatic nccRCC, including but not limited to:
• Papillary RCC, any type
• Unclassified RCC
• Translocation RCC
• Chromophobe RCC
• Collecting duct RCC
• Renal cell carcinoma with 80% or more sarcomatoid features on primary nephrectomy specimen or a biopsy
• Other nccRCC histologies in discussion with principal investigator
• Measurable disease as per RECIST 1.1. See Section 11 for the evaluation of measurable disease.
• Age ≥ 18 years
• ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A)
• Participants must undergo fresh tumor biopsy after registration but prior to the start of treatment unless medically unsafe or not feasible. If a fresh tumor biopsy is not medically safe or not feasible, confirmation of the availability of archival tumor tissue is required. For archival tissue, a recommended minimum of 20 unstained slides should be obtained.
• Normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL

You may not qualify if:

• \- Patients could be untreated or have received prior lines of therapies. Patients who receive prior therapy may receive only one VEGF based therapy. A combination therapy (e.g.
• lenvatinib+everolimus) is considered 1 line of therapy.
• Previous therapy with CD137 agonists and immune checkpoint inhibitors, including but not limited to inhibitors of the PD-1/PD-L1 and/or CTLA-4 axes. Previous treatment with IFNα or IL-2 is allowed if received \> 4 weeks from enrollment.
• Treatment with small molecule tyrosine kinase inhibitors within 2 weeks of enrollment, or any other anticancer agent within 4 weeks of enrollment.
• Prior therapy with cabozantinib
• Patients receiving any other therapeutic investigational agents.
• Treatment with hydroxychloroquine within two weeks of treatment start.
• Radiotherapy for nccRCC within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
• Untreated brain metastases. Patients might be included if they underwent radiation therapy or surgery at least 4 weeks prior enrollment. Stability of the central nervous system disease should be confirmed by brain MRI or CT-scan or as determined by treating investigator. Patients should not be receiving prednisone dose \>10 mg/d at C1D1.
• Other malignancy diagnosed within 2 years of first study treatment unless negligible risk of metastases or death (included but not limited to carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma, or other malignancy not deemed to impact patients 5-year life expectancy).
• Significant cardiovascular disorders including:
• Significant cardiovascular disease including dyspnea of New York Heart Association (NYHA) class II or greater, myocardial infarction within the previous 3 months of first study treatment, unstable arrhythmias, unstable angina. Patients with known coronary artery disease or congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \< 50%, must be on a stable and optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate.
• Uncontrolled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg). Anti-hypertensive therapy is allowed.
• Personal history of hypertensive crisis or hypertensive encephalopathy within the previous 3 months of registration.
• Personal history of stroke or transient ischemic attack within 3 months of registration.

Sponsors & Collaborators

• Bradley A. McGregor, MD: lead
• Bristol-Myers Squibb: collaborator
• Exelixis: collaborator

Study Sites (4)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Brigham & Woman's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

UT Southwestern Medical

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

cabozantinib; Nivolumab; Ipilimumab

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

• Bradley McGregor, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: March 26, 2020
• First Posted: June 2, 2020
• Study Start: November 5, 2020
• Primary Completion (Estimated): June 20, 2026
• Study Completion (Estimated): December 20, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (4)