Clinical trial NCT00563147 (phase 1, status: completed)
Conditions: renal cell carcinoma
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: tivozanib (av-951) plus temsirolimus
SMILES: OCC(C)(CO)C(=O)O[C@@H]1CC[C@@H](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](OC)C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@H]3C(=O)O2)C[C@H]1OC
Eligibility criteria:

        Inclusion Criteria:

          -  ≥ 18-year-old males or females

          -  Histologically confirmed renal cell carcinoma with a clear cell component

          -  Documented progressive disease

          -  Measurable disease by RECIST criteria

          -  No more than 1 prior VEGF receptor targeted therapy; no prior treatment with
             temsirolimus or other drugs targeting the mTOR pathway

          -  Karnofsky performance status > 70%; life expectancy ≥ 3 months

          -  Ability to give written informed consent

        Exclusion Criteria:

          -  Known hypersensitivity to temsirolimus or its metabolites (including sirolimus),
             polysorbate 80, or to any other component of the temsirolimus formulation

          -  Primary CNS malignancies; active CNS metastases

          -  Hematologic malignancies (including leukemia in any form, lymphoma, and multiple
             myeloma)

          -  Any of the following hematologic abnormalities:

               -  Hemoglobin < 9.0 g/dL

               -  ANC < 1500 per mm3

               -  Platelet count < 100,000 per mm3

          -  Any of the following serum chemistry abnormalities:

               -  Fasting serum cholesterol > 350 mg/dL

               -  Fasting triglycerides > 400 mg/dL

               -  Total bilirubin > 1.5 × ULN

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

               -  Serum albumin < 3.0 g/dL

               -  Creatine > 1.5 × ULN (or calculated CLCR <50 mL/min/1.73 m2)

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

          -  Significant cardiovascular disease, including:

               -  Active clinically symptomatic left ventricular failure

               -  Active hypertension (diastolic blood pressure > 100 mmHg). Subjects with a
                  history of hypertension must have been on stable doses of anti-hypertensive drugs
                  for ≥ 4 weeks

               -  Uncontrolled hypertension: Blood pressure >140/90 mmHg on 2 or more
                  antihypertensive medications

               -  Myocardial infarction within 3 months prior to administration of first dose of
                  study drug

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

          -  Pulmonary hypertension or pneumonitis

          -  Serious/active infection; infection requiring parenteral antibiotics

          -  Inadequate recovery from any prior surgical procedure; major surgical procedure within
             6 weeks prior to study entry

          -  Uncontrolled psychiatric disorder, altered mental status precluding informed consent
             or necessary testing

          -  Inability to comply with protocol requirements

          -  Ongoing hemoptysis or history of clinically significant bleeding

          -  Cerebrovascular accident within 12 months of study entry, or peripheral vascular
             disease with claudication on walking less than 1 block

          -  Deep venous thrombosis or pulmonary embolus within 6 months of study entry and/or
             ongoing need for full-dose oral or parenteral anticoagulation

          -  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 are considered by their physician to be <
             30% risk of relapse.

          -  Pregnant or lactating women

          -  Known concomitant genetic or acquired immune suppression disease such as HIV

        Prohibited medications:

          -  VEGF receptor (VEGFR) targeted therapy within 4 weeks prior to and during study

          -  Other signal transduction inhibitors, monoclonal antibodies, etc., within 4 weeks
             prior to and during study

          -  Immunotherapy or biological response modifiers within 4 weeks prior to and during
             study

          -  Systemic hormonal therapy within 4 weeks prior to and during study, with the exception
             of:

               -  Hormonal therapy for appetite stimulation or contraception

               -  Nasal, ophthalmic, and topical glucocorticoid preparations

               -  Oral replacement therapy for adrenal insufficiency

               -  Low-dose maintenance steroid therapy for other conditions

          -  Herbal preparations/supplements (except for a daily multivitamin/mineral supplement
             not containing herbal components) within 2 weeks prior to or during study

          -  Any experimental therapy 4 weeks prior to and during study

          -  Radiotherapy:

               -  At least 2 weeks since prior local radiation therapy (ie, involving <25% of bone
                  marrow) at the time of study entry

               -  At least 4 weeks since prior radiation therapy involving ≥ 25% of bone marrow

          -  Treatment with CYP3A4 inducers or inhibitors during the study