Clinical trial NCT03136627 (phase 1/phase 2, status: active, not recruiting)
Conditions: carcinoma, renal cell
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: tivozanib, nivolumab
SMILES: COC1=C(OC)C=C2C(OC3=CC(Cl)=C(C=C3)N=C(O)N=C3NOC(C)=C3)=CC=NC2=C1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Eligibility criteria:

        Inclusion Criteria:

          1. ≥ 18-year-old

          2. Histologically or cytologically documented renal cell carcinoma with a clear cell
             component, except in Phase 1b, where any histology will be permitted

          3. Metastatic renal cell carcinoma. Measurable or evaluable disease by RECIST 1.1
             criteria

          4. No prior exposure to tivozanib or nivolumab

          5. ECOG performance status ≤ 1 (see Appendix A) and life expectancy ≥ 3 months.

          6. Signed and dated written informed consent

          7. Sexually active pre-menopausal female subjects and female partners of male subjects
             must use adequate contraceptive measures, while on study and for at least 160 days
             after the last dose of study drug. Sexually active male subjects must use adequate
             contraceptive measures, while on study and for at least 160 days after the last dose
             of study drug. All fertile male and female subjects and their partners must agree to
             use a highly effective method of contraception. Effective birth control includes (a)
             intrauterine device (IUD) plus one barrier method; or (b) 2 barrier methods. Effective
             barrier methods are male or female condoms, diaphragms, and spermicides (creams or
             gels that contain a chemical to kill sperm). Note: Oral, implantable, or injectable
             contraceptives may be affected by cytochrome P450 interactions, and are not considered
             effective for this study.

        Exclusion Criteria:

          1. Pregnant or lactating women.

          2. Subjects with symptomatic CNS metastases. Subjects with treated brain metastases that
             have remained stable for at least 3 months without steroids are allowed. Subjects with
             signs or symptoms or history of brain metastasis must have a CT or MRI scan of the
             brain within 1 month prior to the start of protocol therapy. Subjects with spinal cord
             or nerve root compression who have completed treatment at least 4 weeks before the
             start of protocol therapy and are stable without steroid treatment for at least one
             week before start of protocol therapy are allowed. Subjects with leptomeningeal
             metastases are not allowed.

          3. Any of the following hematologic abnormalities:

               -  Hemoglobin < 9.0 g/dL

               -  ANC < 1500 per mm3

               -  Platelet count < 100,000 per mm3

          4. Any of the following serum chemistry abnormalities:

               -  Total bilirubin > 1.5 × ULN (>2.5 mg/dL in patients with Gilbert's syndrome)

               -  AST or ALT > 2.5 × ULN (or > 5 × ULN for subjects with liver metastasis)

               -  Alkaline phosphatase > 2.5 × ULN (or > 5 × ULN for subjects with liver or bone
                  metastasis)

               -  Serum creatinine > 1.5 × ULN

               -  Proteinuria > 2.5 g/24 hours or 3+ with urine dipstick

               -  Any other ³ Grade 3 laboratory abnormality at baseline (other than those listed
                  above)

          5. Significant cardiovascular disease, including:

               -  Clinically symptomatic heart failure. Subjects with a history of heart failure
                  must have an ECHO or MUGA scan to document left ventricular ejection fraction
                  (LVEF) > 45% prior to start of protocol therapy

               -  Uncontrolled hypertension: blood pressure >150/95 mmHg on more than 2
                  antihypertensive medications, on two consecutive measurements obtained at least
                  24 hours apart. Subjects with a history of hypertension must have been on stable
                  doses of anti-hypertensive drugs for ≥ 2 weeks prior to start of protocol
                  therapy.

               -  Myocardial infarction within 3 months prior to start of protocol therapy

          6. Subjects with delayed healing of wounds, ulcers, and/or bone fractures

          7. Serious/active infection or infection requiring parenteral antibiotics

          8. Inadequate recovery from any prior surgical procedure; major surgical procedure within
             4 weeks prior to start of protocol therapy.

          9. Inability to comply with protocol requirements

         10. Subjects with a "currently active" second primary malignancy other than non-melanoma
             skin cancers. Subjects are not considered to have a "currently active" malignancy if
             they have completed anti-cancer therapy and have been disease free for > 2 years.

         11. Known concomitant genetic or acquired immune suppression disease such as HIV

         12. Treatment with systemic hormonal therapy within 3 weeks prior to start of protocol
             therapy, with the exception of:

               -  Hormonal therapy for appetite stimulation or contraception

               -  Nasal, ophthalmic, inhaled and topical steroid preparations

               -  Oral replacement therapy for adrenal insufficiency

               -  Low-dose maintenance steroid therapy (equivalent of prednisone 10mg/day) for
                  other conditions

               -  Hormone replacement therapy

         13. Herbal preparations/supplements (except for a daily multivitamin/mineral supplement
             not containing herbal components) or CYP3A4 inhibitors or inducers (see Appendix B)
             within 2 weeks prior to start of or during protocol therapy.