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
* 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
Brief Title
CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Clear Cell Renal Cell Carcinoma
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
advanced, metastatic RCC
RCC
CB-839
Everolimus
CBE
Glutaminase Inhibitor
Glutaminase
Tumor Metabolism
Glutamine
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03163667
Org Class
Industry
Org Full Name
Calithera Biosciences, Inc
Org Study Id
CX-839-005
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome Description
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.
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.
Outcome Measure
Progression Free Survival (PFS)
Outcome Time Frame
As of the primary data cutoff date of 26 Apr 2019; maximum duration of follow-up for PFS was 11.2 months.
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
As of the data cutoff date of 30 Sep 2020; maximum duration of follow-up for OS was 30.4 months.
Outcome Measure
Overall Survival (OS)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404