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

August 19, 2022 updated by: Calithera Biosciences, Inc

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)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

69

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • The University of Arizona Cancer Center
    • Arkansas
      • Rogers, Arkansas, United States, 72758
        • Highlands Oncology Group
    • California
      • Los Angeles, California, United States, 90017
        • Los Angeles Hematology Oncology Medical Group
      • Los Angeles, California, United States, 90095
        • UCLA Department of Medicine - Hematology/Oncology
      • Stanford, California, United States, 94305
        • Stanford Cancer Center
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists- South
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists- North
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Cancer & Blood Center, LLC
      • Marietta, Georgia, United States, 30060
        • Northwest Georgia Oncology Centers, P.C.
    • Idaho
      • Boise, Idaho, United States, 83712
        • St. Luke's Mountain States Tumor Institute
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Parkview Research Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute, Norton Healthcare Pavilion
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinical Foundation
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Anne Arundel Medical Center Oncology and Hematology
      • Baltimore, Maryland, United States, 21201
        • University of Maryland, Greenebaum Comprehensive Cancer Center
    • Minnesota
      • Saint Louis Park, Minnesota, United States, 55416
        • Metro-Minnesota Community Oncology Research Consortium
    • Missouri
      • Joplin, Missouri, United States, 64804
        • Mercy Clinic Oncology & Hematology
      • Kansas City, Missouri, United States, 64132
        • SCRI HCA Midwest
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Montana
      • Billings, Montana, United States, 59102
        • St. Vincent Frontier Cancer Center
    • Nevada
      • Las Vegas, Nevada, United States, 89148
        • Comprehensive Cancer Centers of Nevada
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center
      • East Setauket, New York, United States, 11733
        • North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists
      • Mineola, New York, United States, 11501
        • NYU Winthrop Hospital - Cancer Clinical Trials Oncology/Hematology
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Medical Center
    • Pennsylvania
      • Lancaster, Pennsylvania, United States, 17604
        • Ann B. Barshinger Cancer Institute / Lancaster General Hospital
      • Monongahela, Pennsylvania, United States, 15063
        • Monongahela Valley Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29414
        • Charleston Hematology Oncology Associates,PA
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • UT/Erlanger Oncology & Hematology
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute - Tennessee Oncology
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas Md Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists
    • Washington
      • Wenatchee, Washington, United States, 98801
        • Wenatchee Valley Hospital and Clinics
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • University of Wisconsin Carbone Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: CB-839 + Everolimus
CB-839 is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles.
Drug: CB-839
oral tablets
Other Names:
  • telaglenastat
Drug: everolimus
oral tablets
Other Names:
  • Afinitor
Placebo Comparator: Placebo + Everolimus
Placebo is administered as oral tablets BID in combination with standard QD everolimus in 28 day cycles.
Drug: Placebo
oral tablets
Drug: everolimus
oral tablets
Other Names:
  • Afinitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: As of the primary data cutoff date of 26 Apr 2019; maximum duration of follow-up for PFS was 11.2 months.

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: As of the data cutoff date of 30 Sep 2020; maximum duration of follow-up for OS was 30.4 months.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Calithera Biosciences, Inc

Investigators

  • Study Director: Sam Whiting, Calithera Biosciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 6, 2017

Primary Completion (Actual)

April 26, 2019

Study Completion (Actual)

June 1, 2020

Study Registration Dates

First Submitted

May 21, 2017

First Submitted That Met QC Criteria

May 21, 2017

First Posted (Actual)

May 23, 2017

Study Record Updates

Last Update Posted (Actual)

September 15, 2022

Last Update Submitted That Met QC Criteria

August 19, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CX-839-005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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