CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)

Clear Cell Renal Cell Carcinoma Clinical Trial

— ENTRATA  

Official title:

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Comparing CB-839 in Combination With Everolimus (CBE) vs. Placebo With Everolimus (PboE) in Patients With Advanced or Metastatic Renal Cell Carcinoma (RCC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03163667
• Other study ID #: CX-839-005
• Status: Completed
• Phase: Phase 2
• Start date: September 6, 2017
• Est. completion date: June 1, 2020

Study information

• Verified date: August 2022
• Source: Calithera Biosciences, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to compare the progression-free survival (PFS) of participants treated with telaglenastat and everolimus versus placebo and everolimus for advanced or metastatic clear cell renal cell carcinoma (ccRCC) previously treated with the following:

• At least 2 lines of therapy, including at least 1 vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI)

• Radiographic progression of metastatic RCC must have occurred (per investigator assessment) on or after the most recent systemic therapy and within 6 months prior to cycle 1 day 1

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: June 1, 2020
• Est. primary completion date: April 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Karnofsky Performance Score (KPS) = 70%

• Estimated Life Expectancy of at least 3 months

• Documented histological or cytological diagnosis of renal cell carcinoma with a clear-cell component.

• Measurable Disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the Investigator

• Must have received at least two prior lines of systemic therapy, including at least one VEGF TKI (e.g., sunitinib, sorafenib, pazopanib, cabozantinib)

a) Radiographic progression of mRCC must have occurred (per investigator assessment) on or after the most recent systemic therapy and within 6 months prior to Cycle 1 Day 1 (C1D1).

• Prior treatment with other anti-cancer therapies including cytokines, monoclonal antibodies, immunotherapies, and cytotoxic chemotherapy is allowed

Exclusion Criteria:

• Prior treatment with mammalian target of rapamycin (mTOR) inhibitors (everolimus or temsirolimus) or CB-839

• Receipt of any anticancer therapy within the following windows before randomization:

• TKI therapy within 2 weeks or 5 half-lives, whichever is longer

• Any type of anti-cancer antibody within 4 weeks

• Cytotoxic chemotherapy within 4 weeks

• Investigational therapy within 4 weeks or 5 half-lives, whichever is longer

• Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization. Patients with clinically relevant ongoing complications from prior radiation therapy are not eligible.

• Unable to receive medications orally (PO) or any condition that may prevent adequate absorption of oral study medication

• Major surgery within 28 days prior to randomization

• Patients with active and/or untreated central nervous system (CNS) cancer are not eligible. Patients with treated brain metastasis must have 1) documented radiographic stability of at least 4 weeks duration demonstrated on baseline contrast-enhanced CNS imaging (eg contrast-enhanced magnetic resonance imaging [MRI] of the brain) prior to randomization and 2) must be symptomatically stable and off steroids for at least 2 weeks before randomization.

• Requirement for continued proton pump inhibitor after randomization

• Chronic treatment with corticosteroids or other immunosuppressive agents except (i) inhaled or topical steroids or replacement dose corticosteroids equivalent to = 10 mg prednisone and (ii) patients receiving physiological doses of hydrocortisone for adrenal insufficiency

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma

Intervention

Drug:
• Placebo
oral tablets
• CB-839
oral tablets
• everolimus
oral tablets

Locations

Country	Name	City	State
United States	Anne Arundel Medical Center Oncology and Hematology	Annapolis	Maryland
United States	University Cancer & Blood Center, LLC	Athens	Georgia
United States	University of Maryland, Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	St. Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Montefiore Medical Center	Bronx	New York
United States	Charleston Hematology Oncology Associates,PA	Charleston	South Carolina
United States	UT/Erlanger Oncology & Hematology	Chattanooga	Tennessee
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists	East Setauket	New York
United States	Florida Cancer Specialists- South	Fort Myers	Florida
United States	Parkview Research Center	Fort Wayne	Indiana
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Mercy Clinic Oncology & Hematology	Joplin	Missouri
United States	SCRI HCA Midwest	Kansas City	Missouri
United States	Ann B. Barshinger Cancer Institute / Lancaster General Hospital	Lancaster	Pennsylvania
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Los Angeles Hematology Oncology Medical Group	Los Angeles	California
United States	UCLA Department of Medicine - Hematology/Oncology	Los Angeles	California
United States	Norton Cancer Institute, Norton Healthcare Pavilion	Louisville	Kentucky
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	NYU Winthrop Hospital - Cancer Clinical Trials Oncology/Hematology	Mineola	New York
United States	Monongahela Valley Hospital	Monongahela	Pennsylvania
United States	Sarah Cannon Research Institute - Tennessee Oncology	Nashville	Tennessee
United States	Ochsner Clinical Foundation	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Highlands Oncology Group	Rogers	Arkansas
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro-Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Florida Cancer Specialists- North	Saint Petersburg	Florida
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Stanford Cancer Center	Stanford	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Calithera Biosciences, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS was defined as the time from randomization to the date of documented disease progression (assessed by Investigator per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) within 2 scheduled scan intervals following previous evaluable radiologic tumor assessment or death for any cause, whichever occurred first. Participants with no documentation of disease progression or death on-study were censored at the date of last available tumor assessment.; Progressive Disease (PD) per RECIST 1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.	As of the primary data cutoff date of 26 Apr 2019; maximum duration of follow-up for PFS was 11.2 months.
Secondary	Overall Survival (OS)	Overall survival is defined as the time from randomization to the date of death from any cause. Participants with no documentation of death on-study were censored at the date at which they were last known to be alive.	As of the data cutoff date of 30 Sep 2020; maximum duration of follow-up for OS was 30.4 months.

External Links

•   Calithera Biosciences Company website