dose escalation safety study of tl32711 in adults with refractory solid tumors or lymphoma

Conditions: Cancer

Summary: a phase 1 open-label, non-randomized dose escalation study to determine the maximum tolerated dose (mtd) and characterize the safety and tolerability of birinapant (tl32711).

the purpose of this phase 1 open-label, non-randomized dose escalation study is to determine the maximum tolerated dose (mtd) and characterize the safety and tolerability of birinapant (tl32711) when administered as a 30 minute intravenous infusion once weekly for three weeks per repeated 4 week intervals in subjects with refractory solid tumors or lymphoma. additionally study will assess anti-tumor activity, pharmacokinetics, and exploratory biomarkers as a measurement of pharmacodynamic effects.

Eligibility criteria:
key inclusion criteria: * advanced metastatic or unresectable malignancy that is refractory to currently available standard therapies or no effective therapy exists. the subject's malignancy must be confirmed by prior pathologic study. * evaluable disease (measurable or non-measurable) by response evaluation criteria in solid tumors (recist, version 1.1) or revised response criteria for malignant lymphoma (rrcml) (cheson 2007). * life expectancy greater than 3 months. * eastern cooperative oncology group (ecog) performance status of ≤ 2. * adequate renal function, defined as serum creatinine ≤ 1.5 x upper limit of normal (uln), or calculated creatinine clearance ≥ 60 ml/min. * adequate hepatic function, defined as aspartate aminotransferase (ast) and alanine aminotransferase (alt) levels ≤ 3 x uln and total bilirubin \< 1.5 x uln. * adequate bone marrow function, defined as absolute neutrophil (anc) ≥ 1,500/mm3 (≥1.5 x106/l), platelet count ≥ 75,000/mm3 (≥ 75 x106/l), and hemoglobin ≥ 10 mg/dl in the absence of transfusion. key exclusion criteria: * recent anti-cancer treatment defined as: * standard or investigational anti-cancer therapy within 4 weeks prior to first dose of tl32711. exception: continued hormonal interventions for sensitive diseases. * radiation therapy within 2 weeks prior to the first dose of tl32711. * clinically significant pulmonary illness resulting in grade ≥ 2 hypoxia (national cancer institute common terminology criteria for adverse events \[nci ctcae, v4\]) or any requirement for supplemental oxygen, or pulse oximetry less than 90% saturation on room air. * symptomatic or uncontrolled brain metastases requiring current treatment (less than 4 weeks from last cranial radiation or 2 weeks from last steroids). * impaired cardiac function or clinically significant cardiac disease. * ongoing auto-immune disease or with history of an auto-immune disease within the past 5 years. auto-immune disease include but are not limited to systemic lupus erythematosis, scleroderma, rheumatoid arthritis, psoriasis, psoriatic arthritis, ulcerative colitis and regional enteritis (crohn's disease). * systemic or chronic topical corticosteroids or immunosuppressive therapy within 4 weeks prior to study entry or anticipated need of systemic corticosteroids or immunosuppressive therapy during study participation. * skin lesions of grade ≥ 2 severity (nci ctcae v4), except alopecia. * lack of recovery of prior adverse events to grade ≤1 severity (nci ctcae v 4) (except alopecia or neuropathy) due to medications administered prior to the first dose of tl32711.