CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)
ENTRATA
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)
1 other identifier
interventional
69
1 country
38
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2017
38 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 21, 2017
CompletedFirst Posted
Study publicly available on registry
May 23, 2017
CompletedStudy Start
First participant enrolled
September 6, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 26, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2020
CompletedResults Posted
Study results publicly available
September 15, 2022
CompletedSeptember 15, 2022
August 1, 2022
1.6 years
May 21, 2017
July 18, 2022
August 19, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (1)
Overall Survival (OS)
As of the data cutoff date of 30 Sep 2020; maximum duration of follow-up for OS was 30.4 months.
Study Arms (2)
CB-839 + Everolimus
ACTIVE COMPARATORCB-839 is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles.
Placebo + Everolimus
PLACEBO COMPARATORPlacebo is administered as oral tablets BID in combination with standard QD everolimus in 28 day cycles.
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (38)
The University of Arizona Cancer Center
Tucson, Arizona, 85724, United States
Highlands Oncology Group
Rogers, Arkansas, 72758, United States
Los Angeles Hematology Oncology Medical Group
Los Angeles, California, 90017, United States
UCLA Department of Medicine - Hematology/Oncology
Los Angeles, California, 90095, United States
Stanford Cancer Center
Stanford, California, 94305, United States
Florida Cancer Specialists- South
Fort Myers, Florida, 33901, United States
Florida Cancer Specialists- North
St. Petersburg, Florida, 33705, United States
University Cancer & Blood Center, LLC
Athens, Georgia, 30607, United States
Northwest Georgia Oncology Centers, P.C.
Marietta, Georgia, 30060, United States
St. Luke's Mountain States Tumor Institute
Boise, Idaho, 83712, United States
Northwestern University
Chicago, Illinois, 60611, United States
Parkview Research Center
Fort Wayne, Indiana, 46845, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
Norton Cancer Institute, Norton Healthcare Pavilion
Louisville, Kentucky, 40202, United States
Ochsner Clinical Foundation
New Orleans, Louisiana, 70121, United States
Anne Arundel Medical Center Oncology and Hematology
Annapolis, Maryland, 21401, United States
University of Maryland, Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201, United States
Metro-Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416, United States
Mercy Clinic Oncology & Hematology
Joplin, Missouri, 64804, United States
SCRI HCA Midwest
Kansas City, Missouri, 64132, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
St. Vincent Frontier Cancer Center
Billings, Montana, 59102, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89148, United States
North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists
East Setauket, New York, 11733, United States
NYU Winthrop Hospital - Cancer Clinical Trials Oncology/Hematology
Mineola, New York, 11501, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
Montefiore Medical Center
The Bronx, New York, 10461, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219, United States
Ann B. Barshinger Cancer Institute / Lancaster General Hospital
Lancaster, Pennsylvania, 17604, United States
Monongahela Valley Hospital
Monongahela, Pennsylvania, 15063, United States
Charleston Hematology Oncology Associates,PA
Charleston, South Carolina, 29414, United States
UT/Erlanger Oncology & Hematology
Chattanooga, Tennessee, 37403, United States
Sarah Cannon Research Institute - Tennessee Oncology
Nashville, Tennessee, 37203, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
Wenatchee Valley Hospital and Clinics
Wenatchee, Washington, 98801, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53705, United States
Related Publications (2)
Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.
PMID: 39462179DERIVEDLee CH, Motzer R, Emamekhoo H, Matrana M, Percent I, Hsieh JJ, Hussain A, Vaishampayan U, Liu S, McCune S, Patel V, Shaheen M, Bendell J, Fan AC, Gartrell BA, Goodman OB, Nikolinakos PG, Kalebasty AR, Zakharia Y, Zhang Z, Parmar H, Akella L, Orford K, Tannir NM. Telaglenastat plus Everolimus in Advanced Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled, Phase II ENTRATA Trial. Clin Cancer Res. 2022 Aug 2;28(15):3248-3255. doi: 10.1158/1078-0432.CCR-22-0061.
PMID: 35576438DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Calithera Biosciences, Inc
Study Officials
- STUDY DIRECTOR
Sam Whiting
Calithera Biosciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Double blinded, placebo-controlled
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 21, 2017
First Posted
May 23, 2017
Study Start
September 6, 2017
Primary Completion
April 26, 2019
Study Completion
June 1, 2020
Last Updated
September 15, 2022
Results First Posted
September 15, 2022
Record last verified: 2022-08
Data Sharing
- IPD Sharing
- Will not share