Dose Escalation Safety Study of TL32711 in Adults With Refractory Solid Tumors or Lymphoma
Study Details
Study Description
Brief 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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Birinapant (TL32711)
|
Drug: Birinapant (TL32711)
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
Other Names:
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Outcome Measures
Primary Outcome Measures
- Define the MTD [4 weeks (Cycle 1)]
Secondary Outcome Measures
- 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]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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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.
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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).
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Life expectancy greater than 3 months.
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Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
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Adequate renal function, defined as serum creatinine ≤ 1.5 X upper limit of normal (ULN), or calculated creatinine clearance ≥ 60 ml/min.
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Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 3 X ULN and total bilirubin < 1.5 X ULN.
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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:
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Recent anti-cancer treatment defined as:
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Standard or investigational anti-cancer therapy within 4 weeks prior to first dose of TL32711. Exception: continued hormonal interventions for sensitive diseases.
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Radiation therapy within 2 weeks prior to the first dose of TL32711.
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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.
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Symptomatic or uncontrolled brain metastases requiring current treatment (less than 4 weeks from last cranial radiation or 2 weeks from last steroids).
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Impaired cardiac function or clinically significant cardiac disease.
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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).
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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.
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Skin lesions of Grade ≥ 2 severity (NCI CTCAE v4), except alopecia.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 2 | University of Pennsylvania Abramson Cancer Center | Philadelphia | Pennsylvania | United States | 19104 |
| 3 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
Sponsors and Collaborators
- TetraLogic Pharmaceuticals
Investigators
- Principal Investigator: Ravi Amaravadi, MD, University of Pennsylvania, Abramson Cancer Center
- Principal Investigator: Lainie P Martin, MD, Fox Chase Cancer Center
- Principal Investigator: Alex Adjei, MD, PhD, Roswell Park Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TL32711-FIH-007-PTL-F