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

Phase 2

Completed

• Conditions: Advanced Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma
• Interventions: Drug: CB-839; Drug: Cabozantinib; Drug: Placebo

• Registration Number: NCT03428217
• Lead Sponsor: Calithera Biosciences, Inc

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-02-05
• Study First Submitted QC: 2018-02-05
• Study First Posted: 2018-02-09
• Study Start: 2018-04-24
• Primary Completion: 2020-08-31
• Study Completion: 2021-07-16
• Disposition First Submitted: 2021-08-16
• Results First Submitted: 2023-01-25
• Status Verified: 2023-02
• Results First Submitted QC: 2023-02-21
• Last Update Submitted: 2023-02-21
• Results First Posted: 2023-03-20
• Disposition First Posted: 2023-03-20
• Last Update Posted: 2023-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 444

Inclusion Criteria

1. Documented histological or cytological diagnosis of renal cell carcinoma with a clear-cell component
2. Adult patients
3. Karnofsky Performance Score (KPS) ≥ 70%
4. Measurable Disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
5. 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
6. Adequate hepatic, renal, cardiac and hematologic function

Exclusion Criteria

1. Prior treatment with cabozantinib (or other mesenchymal-epithelial transition [MET] inhibitor) or CB-839
2. Receipt of other anticancer therapy within 2-6 weeks, depending on the treatment
3. Untreated or active brain metastases or central nervous system cancer, as defined per protocol
4. Prior gastric surgery, small bowel resection, or other conditions that may impede adequate absorption of oral study drug
5. Known active infection with human immunodeficiency virus (HIV), Hepatitis B or C virus
6. Inability to discontinue proton-pump-inhibitor use before randomization
7. Patients who are pregnant or lactating

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pbo-Cabo	Placebo	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.
CB-Cabo	CB-839	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.
Pbo-Cabo	Cabozantinib	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.
CB-Cabo	Cabozantinib	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.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) as Assessed by the Independent Radiology Committee (IRC)	Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.14 months.	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for OS was 25.86 months.	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.
PFS as Assessed by the Investigator	Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.64 months.	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.

Trial Locations

Locations (132)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Mayo Clinic Cancer Center; 🇺🇸 Phoenix, Arizona, United States

The University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute; 🇺🇸 Los Angeles, California, United States

Stanford Cancer Center; 🇺🇸 Palo Alto, California, United States

Salinas Valley Memorial Healthcare System; 🇺🇸 Salinas, California, United States

St. Joseph Heritage Healthcare; 🇺🇸 Santa Rosa, California, United States

Penrose Cancer Center, Research Department; 🇺🇸 Colorado Springs, Colorado, United States

Georgetown University Medical Center; 🇺🇸 Washington, District of Columbia, United States

Florida Cancer Specialists; 🇺🇸 Saint Petersburg, Florida, United States

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