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

NCT ID: NCT03163667

Last Updated: 2022-09-15

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

69 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-06

Study Completion Date

2020-06-01

Brief Summary

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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

Detailed Description

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Conditions

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Clear Cell Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a double blinded placebo-controlled study where participants will be randomized 2:1 to either CB-839 plus everolimus (CBE) or placebo plus everolimus (PboE)
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double blinded, placebo-controlled

Study Groups

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CB-839 + Everolimus

CB-839 is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles.

Group Type ACTIVE_COMPARATOR

CB-839

Intervention Type DRUG

oral tablets

everolimus

Intervention Type DRUG

oral tablets

Placebo + Everolimus

Placebo is administered as oral tablets BID in combination with standard QD everolimus in 28 day cycles.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

oral tablets

everolimus

Intervention Type DRUG

oral tablets

Interventions

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Placebo

oral tablets

Intervention Type DRUG

CB-839

oral tablets

Intervention Type DRUG

everolimus

oral tablets

Intervention Type DRUG

Other Intervention Names

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telaglenastat Afinitor

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Calithera Biosciences, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sam Whiting

Role: STUDY_DIRECTOR

Calithera Biosciences

Locations

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The University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

Highlands Oncology Group

Rogers, Arkansas, United States

Site Status

Los Angeles Hematology Oncology Medical Group

Los Angeles, California, United States

Site Status

UCLA Department of Medicine - Hematology/Oncology

Los Angeles, California, United States

Site Status

Stanford Cancer Center

Stanford, California, United States

Site Status

Florida Cancer Specialists- South

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists- North

St. Petersburg, Florida, United States

Site Status

University Cancer & Blood Center, LLC

Athens, Georgia, United States

Site Status

Northwest Georgia Oncology Centers, P.C.

Marietta, Georgia, United States

Site Status

St. Luke's Mountain States Tumor Institute

Boise, Idaho, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Parkview Research Center

Fort Wayne, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Norton Cancer Institute, Norton Healthcare Pavilion

Louisville, Kentucky, United States

Site Status

Ochsner Clinical Foundation

New Orleans, Louisiana, United States

Site Status

Anne Arundel Medical Center Oncology and Hematology

Annapolis, Maryland, United States

Site Status

University of Maryland, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status

Metro-Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, United States

Site Status

Mercy Clinic Oncology & Hematology

Joplin, Missouri, United States

Site Status

SCRI HCA Midwest

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

St. Vincent Frontier Cancer Center

Billings, Montana, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists

East Setauket, New York, United States

Site Status

NYU Winthrop Hospital - Cancer Clinical Trials Oncology/Hematology

Mineola, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

Ann B. Barshinger Cancer Institute / Lancaster General Hospital

Lancaster, Pennsylvania, United States

Site Status

Monongahela Valley Hospital

Monongahela, Pennsylvania, United States

Site Status

Charleston Hematology Oncology Associates,PA

Charleston, South Carolina, United States

Site Status

UT/Erlanger Oncology & Hematology

Chattanooga, Tennessee, United States

Site Status

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Utah Cancer Specialists

Salt Lake City, Utah, United States

Site Status

Wenatchee Valley Hospital and Clinics

Wenatchee, Washington, United States

Site Status

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 39462179 (View on PubMed)

Lee 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.

Reference Type DERIVED
PMID: 35576438 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CX-839-005

Identifier Type: -

Identifier Source: org_study_id

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