CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)
Condition: Clear Cell Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Placebo; CB-839; everolimus
Intervention description: oral tablets; oral tablets; oral tablets
Intervention MeSH terms: Everolimus
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 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
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: advanced, metastatic RCC; RCC; CB-839; Everolimus; CBE; Glutaminase Inhibitor; Glutaminase; Tumor Metabolism; Glutamine

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
    

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