CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC) (ENTRATA)
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| ClinicalTrials.gov Identifier: NCT03163667 |
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Recruitment Status :
Completed
First Posted : May 23, 2017
Results First Posted : September 15, 2022
Last Update Posted : September 15, 2022
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Clear Cell Renal Cell Carcinoma | Drug: Placebo Drug: CB-839 Drug: everolimus | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 69 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| 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) |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Double blinded, placebo-controlled |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | September 6, 2017 |
| Actual Primary Completion Date : | April 26, 2019 |
| Actual Study Completion Date : | June 1, 2020 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: CB-839
oral tablets
Other Name: telaglenastat Drug: everolimus oral tablets
Other Name: Afinitor |
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Placebo Comparator: Placebo + Everolimus
Placebo is administered as oral tablets BID in combination with standard QD everolimus in 28 day cycles.
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Drug: Placebo
oral tablets Drug: everolimus oral tablets
Other Name: Afinitor |
- 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.
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03163667
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| Study Director: | Sam Whiting | Calithera Biosciences |
Documents provided by Calithera Biosciences, Inc:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Calithera Biosciences, Inc |
| ClinicalTrials.gov Identifier: | NCT03163667 |
| Other Study ID Numbers: |
CX-839-005 |
| First Posted: | May 23, 2017 Key Record Dates |
| Results First Posted: | September 15, 2022 |
| Last Update Posted: | September 15, 2022 |
| Last Verified: | August 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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advanced, metastatic RCC RCC CB-839 Everolimus CBE |
Glutaminase Inhibitor Glutaminase Tumor Metabolism Glutamine |
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Carcinoma Carcinoma, Renal Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases |
Kidney Diseases Urologic Diseases Male Urogenital Diseases Everolimus MTOR Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents |