Clear Cell Renal Cell CarcinomaPhase 2ENTRATANCT03163667

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

A Phase 2 study testing CB-839 and everolimus in people with Clear Cell Renal Cell Carcinoma, run by Calithera Biosciences, Inc at 38 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Clear Cell Renal Cell Carcinoma
What is being tested?: CB-839 and everolimus
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 69 participants
Where: 38 sitesUnited States
Study dates: 6 Sep 2017to 1 Jun 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)
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

Who cannot join

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

Show all 12Show fewer

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

Trial locations and contacts

38 sites in 1 country.

City, postcode or hospital

38 sites in 1 country

United States38 sites

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

Other trials in United States

About this study

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)

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

Conditions: Clear Cell Renal Cell Carcinoma
Being tested: Placebo, CB-839, everolimus
Keywords: advanced, metastatic RCC, RCC, CB-839, Everolimus, CBE, Glutaminase Inhibitor, Glutaminase, Tumor Metabolism, Glutamine
Medical subject headings: Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
oral tablets
CB-839Drug
Also called telaglenastat
oral tablets
everolimusDrug
Also called Afinitor
oral tablets

Study groups in NCT03163667
Study group	Role	What they receive
CB-839 + Everolimus	Active comparator	CB-839 is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles. Receives: Drug: CB-839; Drug: everolimus
Placebo + Everolimus	Placebo comparator	Placebo is administered as oral tablets BID in combination with standard QD everolimus in 28 day cycles. Receives: Drug: Placebo; Drug: everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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)
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.
Measured: As of the data cutoff date of 30 Sep 2020; maximum duration of follow-up for OS was 30.4 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Sep 20171 Jun 2020

First posted23 May 2017
Study start6 Sep 2017
Primary completion26 Apr 2019
Study completion1 Jun 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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)
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 69 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03163667
Sponsor's protocol ID: CX-839-005
Acronym: ENTRATA
Status last verified: Aug 2022
First submitted: 21 May 2017
Last updated: 15 Sep 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 39462179
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.
PubMed 35576438

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
Localized Clear Cell Renal Cell Carcinoma
Active, not recruitingPhase 1/2
Phase 1b/2 Trial of Ipilimumab, Nivolumab, and Ciforadenant (Adenosine A2a Receptor Antagonist) in First-line Advanced Renal Cell Carcinoma.
Renal Cell Carcinoma

All Clear Cell Renal Cell Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT03163667
Acronym / sponsor ID: ENTRATA / CX-839-005
Conditions: Clear Cell Renal Cell Carcinoma
Keywords: advanced, metastatic RCC, RCC, CB-839, Everolimus, CBE, Glutaminase Inhibitor, Glutaminase, Tumor Metabolism
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 69 participants (actual)
Lead sponsor: Calithera Biosciences, IncIndustry (pharma, biotech, devices)
Study start: 6 Sep 2017 (actual)
Primary completion: 26 Apr 2019 (actual)
Study completion: 1 Jun 2020 (actual)
First posted: 23 May 2017 (actual)
Results: Posted 15 Sep 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
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)

Arm	Type	Receives
CB-839 + Everolimus	Active comparator	Drug: CB-839, Drug: everolimusCB-839 is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles.
Placebo + Everolimus	Placebo comparator	Drug: Placebo, Drug: everolimusPlacebo is administered as oral tablets BID in combination with standard QD everolimus in 28 day cycles.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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)

Key exclusion criteria (12 listed)

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:
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Placebooral tablets	Drug	Placebo + Everolimus
CB-839Also: telaglenastatoral tablets	Drug	CB-839 + Everolimus
everolimusAlso: Afinitororal tablets	Drug	CB-839 + Everolimus, Placebo + Everolimus

Primary outcome

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.

1 secondary outcome

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.

Results and safety

Results posted to the registry on 15 Sep 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo + Everolimus	23	0
CB-839 + Everolimus	46	0

Primary outcome: 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.. Median (95% Confidence Interval). Unit: months

Measure	Placebo + Everolimus n = 23	CB-839 + Everolimus n = 46
Value	1.91 (1.87 to 8.28)	3.81 (2.40 to 7.43)

Placebo + Everolimus vs CB-839 + Everolimus: Hazard Ratio (HR): 0.64 (95% CI 0.34 to 1.20), p = 0.07905, Log Rank
Placebo + Everolimus vs CB-839 + Everolimus: Hazard Ratio (HR): 0.69 (95% CI 0.37 to 1.28), p = 0.1184, Log Rank

Population analysed: Intent to Treat Population: all randomized participants.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo + Everolimus	8 of 23 (34.8%)	23 of 23 (100%)	15 of 23
CB-839 + Everolimus	21 of 46 (45.7%)	45 of 46 (97.8%)	27 of 46

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39462179Aden 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.
Derived from this study: PubMed 35576438Lee 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.
Individual participant dataSharing planned: No

Related trials for Clear Cell Renal Cell Carcinoma

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
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Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
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Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sam Whiting study director

Calithera Biosciences

38 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CB-839 and everolimus in people with Clear Cell Renal Cell Carcinoma, run by Calithera Biosciences, Inc at 38 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03163667, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2022.