Dose Escalation Safety Study of TL32711 in Adults With Refractory Solid Tumors or Lymphoma

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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A Phase 1, Open-Label, Non-randomized, Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TL32711 in Adults With Refractory Solid Tumors or Lymphoma

Conditions
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Cancer

Intervention / Treatment
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* Drug: Birinapant (TL32711)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Birinapant (TL32711)<br> | Drug: Birinapant (TL32711)<br>* 30 minute intravenous (IV) infusion administered once weekly for three consecutive weeks followed by a one week off (Cycle) repeated every 4 weeks as tolerated<br>* Other names: NSC 756502;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define the MTD |  | 4 weeks (Cycle 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST)/Revised Response Criteria Malignant Lymphoma |  | Every 8 weeks (2 cycles) while on treatment | 
| Translational biomarkers and pharmacokinetics |  | First and third dose of Cycle 1 and after every two cycles (biomarkers only) while on treatment |