Clinical trial NCT03163667 (phase 2, status: completed)
Conditions: clear cell renal cell carcinoma
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: cb-839 plus everolimus, placebo plus everolimus
SMILES: [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC, [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC
Eligibility criteria:

        Inclusion Criteria:

          -  Karnofsky Performance Score (KPS) ≥ 70%

          -  Estimated Life Expectancy of at least 3 mo

          -  Documented histological or cytological diagnosis of renal cell carcinoma with a
             clear-cell component.

          -  Measurable Disease per RECIST 1.1 as determined by the Investigator

          -  Must have received at least two prior lines of systemic therapy, including at least
             one VEGFR-targeting 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 mo prior to C1D1.

          -  Prior treatment with other anti-cancer therapies including cytokines, monoclonal
             antibodies, immunotherapies, and cytotoxic chemotherapy is allowed

        Exclusion Criteria:

          -  Prior treatment with 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 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 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