CANTATA: CB-839 With Cabozantinib vs. Cabozantinib With Placebo in Patients With Metastatic Renal Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
Tthe primary objective of this study is to compare blinded Independent Radiology Committee (IRC)-adjudicated progression free survival (PFS) of patients treated with CB-839 + cabozantinib (CB-Cabo) versus placebo + cabozantinib (Pbo-Cabo) for advanced or metastatic clear-cell RCC (ccRCC).

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial Comparing CB-839 in Combination With Cabozantinib (CB-Cabo) vs. Placebo With Cabozantinib (Pbo-Cabo) in Patients With Advanced or Metastatic Renal Cell Carcinoma (RCC)

Conditions
-----------------
Advanced Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: CB-839
* Drug: Cabozantinib
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented histological or cytological diagnosis of renal cell carcinoma with a clear-cell component Adult patients Karnofsky Performance Score (KPS) ≥ 70% Measurable Disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) 1-2 lines of prior therapy for advanced or metastatic renal cell carcinoma (RCC) including one anti-angiogenic therapy (any vascular endothelial growth factor [VEGF] pathway-targeted agent used either as monotherapy or as a component of a combination regimen) OR the combination regimen of nivolumab + ipilimumab Adequate hepatic, renal, cardiac and hematologic function Exclusion Criteria: Prior treatment with cabozantinib (or other mesenchymal-epithelial transition [MET] inhibitor) or CB-839 Receipt of other anticancer therapy within 2-6 weeks, depending on the treatment Untreated or active brain metastases or central nervous system cancer, as defined per protocol Prior gastric surgery, small bowel resection, or other conditions that may impede adequate absorption of oral study drug Known active infection with human immunodeficiency virus (HIV), Hepatitis B or C virus Inability to discontinue proton-pump-inhibitor use before randomization Patients who are pregnant or lactating

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a double blinded placebo-controlled study where patients will be randomized 1:1 to either CB-839 (telaglenastat) plus cabozantinib or placebo plus cabozantinib
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Pbo-Cabo<br>Placebo twice daily (BID) + cabozantinib (60 mg once daily [QD]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first. | Drug: Cabozantinib<br>* Oral receptor tyrosine kinase inhibitor<br>* Other names: Cabometriq;Drug: Placebo<br>* Placebo tablets<br>|
| Experimental: CB-Cabo<br>CB-839 800 mg BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first. | Drug: CB-839<br>* Oral glutaminase inhibitor<br>* Other names: telaglenastat;Drug: Cabozantinib<br>* Oral receptor tyrosine kinase inhibitor<br>* Other names: Cabometriq;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) as Assessed by the Independent Radiology Committee (IRC) | PFS is defined as the time from randomization to the occurrence of disease progression as assessed by the IRC using RECIST v1.1 or death from any cause, whichever occurs first. Subjects not experiencing disease progression or death at the time of analysis of PFS will be censored at the date of the last evaluable radiographic disease assessment. RECIST v1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): 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. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.14 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. Estimated from Kaplan-Meier methodology. 95% confidence interval (CI) based on Brookmeyer-Crowley methodology. | Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for OS was 25.86 months. | 
| PFS as Assessed by the Investigator | PFS is defined as the time from randomization to the occurrence of disease progression as assessed by the IRC using RECIST v1.1 or death from any cause, whichever occurs first. Subjects not experiencing disease progression or death at the time of analysis of PFS will be censored at the date of the last evaluable radiographic disease assessment. RECIST v1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): 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. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.64 months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tumor Metabolism, RCC, Glutaminase Inhibitor, CB-839, CANTATA, TKI, Tyrosine Kinase Inhibitor, cabozantinib, Cabometyx, Cometriq, glutaminase, glutamine, renal cell, clear cell, kidney cancer, cMET, MET, HGFR, telaglenastat