Clinical trial NCT03163667: CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clear Cell Renal Cell Carcinoma
Keywords: advanced, metastatic RCC
RCC
CB-839
Everolimus
CBE
Glutaminase Inhibitor
Glutaminase
Tumor Metabolism
Glutamine
Lead sponsor: Calithera Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2017-05-23
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: As of the primary data cutoff date of 26 Apr 2019; maximum duration of follow-up for PFS was 11.2 months.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: As of the data cutoff date of 30 Sep 2020; maximum duration of follow-up for OS was 30.4 months.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Los Angeles
country: United States
facility: Los Angeles Hematology Oncology Medical Group
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine - Hematology/Oncology
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists- South
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists- North
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, P.C.
state: Georgia
city: Boise
country: United States
facility: St. Luke's Mountain States Tumor Institute
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute, Norton Healthcare Pavilion
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinical Foundation
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Medical Center Oncology and Hematology
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Comprehensive Cancer Center
state: Maryland
city: Saint Louis Park
country: United States
facility: Metro-Minnesota Community Oncology Research Consortium
state: Minnesota
city: Joplin
country: United States
facility: Mercy Clinic Oncology & Hematology
state: Missouri
city: Kansas City
country: United States
facility: SCRI HCA Midwest
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center
state: Montana
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists
state: New York
city: Mineola
country: United States
facility: NYU Winthrop Hospital - Cancer Clinical Trials Oncology/Hematology
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Lancaster
country: United States
facility: Ann B. Barshinger Cancer Institute / Lancaster General Hospital
state: Pennsylvania
city: Monongahela
country: United States
facility: Monongahela Valley Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates,PA
state: South Carolina
city: Chattanooga
country: United States
facility: UT/Erlanger Oncology & Hematology
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital and Clinics
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: Calithera Biosciences
name: Sam Whiting
role: STUDY_DIRECTOR
References:
citation: 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.