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

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

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).

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: Birinapant (TL32711)

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 Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Abramson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: NSC 756502

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: 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 record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: October 8, 2009
• First Submitted That Met QC Criteria: October 9, 2009
• First Posted (Estimate): October 12, 2009

Study Record Updates

• Last Update Posted (Estimate): March 3, 2016
• Last Update Submitted That Met QC Criteria: March 1, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: TL32711-FIH-007-PTL-F

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No