CANTATA: CB-839 With Cabozantinib vs. Cabozantinib With Placebo in Patients With Metastatic Renal Cell Carcinoma
Condition: Advanced Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: CB-839; Cabozantinib; Placebo
Intervention description: Oral glutaminase inhibitor; Oral receptor tyrosine kinase inhibitor; Placebo tablets
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Participants, care providers, investigators and outcomes assessors are blinded to treatment. Progression free survival (PFS) will be assessed by a blinded Independent Radiology Committee for the primary endpoint of the study.
Enrollment: 444.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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

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).
    

Eligibility criteria:

        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