Dose Escalation, Combination Chemotherapy Safety Study of Birinapant (TL32711), in Subjects With Advanced or Metastatic Solid Tumors

Cancer Clinical Trial

Official title:

A Phase 1B/2A, Open-label, Non-randomized, Multi-arm Study of TL32711 in Combination With Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01188499
• Other study ID #: TL32711-POC-0078-PTL
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 23, 2010
• Last updated: March 1, 2016
• Start date: October 2010
• Est. completion date: March 2014

Study information

• Verified date: March 2016
• Source: TetraLogic Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a dose escalation safety study of birinapant (TL32711) in combination with chemotherapy in subjects with advanced or metastatic solid tumors.

Description:

The purpose of this study is to determine the safety and maximum tolerated dose of birinapant (TL32711) as a 30 minute intravenous infusion once a week, for 2 consecutive weeks, when combined with standard regimens of chemotherapy in subjects with advanced or metastatic solid tumors. Additionally the study will assess anti-tumor activity, pharmacokinetics, and exploratory biomarkers as a measurement of pharmacodynamic effects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: March 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed advanced or metastatic malignancy for which the proposed chemotherapy regimen is appropriate in the judgment of the Investigator.

• Prior therapy in dose-escalation and expansion cohorts:

• Dose-escalation cohorts: Subjects may be naïve or may have received prior therapy with the specific chemotherapeutic agent(s) being recommended in the combination arm, provided the subject did not experience life-threatening toxicity attributed to the specific agent(s).

• Expansion cohorts: Subjects have advanced colorectal cancer that had been previously determined to be KRAS mutant. Subjects naïve to irinotecan may be enrolled, and the KRAS mutation status may be wild type or mutant. Subjects previously treated with an irinotecan containing regimen may be enrolled only if they have been previously determined to be KRAS wild type. The irinotecan regimen must not have been associated with life threatening adverse events.

• Subjects evaluated for Arm 5 (liposomal doxorubicin) may not have received >300 mg/m2 cumulative dose of anthracycline.

• Life expectancy >3 months.

• Eastern Cooperative Oncology Group (ECOG) performance status of =2.

• Adequate renal function

• Adequate hepatic function

• Adequate bone marrow function

• Women of childbearing potential must have a negative serum pregnancy test.

• Women of childbearing potential must agree to use 2 methods of adequate contraception (ie, hormonal and barrier method) prior to enrollment, during the study, and for a period of 30 days following the last dose of TL32711. Males who are sexually active must agree to use a condom during the study and for a period of 30 days following the last dose of TL32711, and if their partner is of childbearing potential, she must agree to use a secondary method of contraception (ie, hormonal, intrauterine device, barrier) during the study and for a period of 30 days following the last dose of TL32711.

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 prostate cancer.

• Radiation therapy within 2 weeks prior to the first dose of TL32711.

• Major surgery within 4 weeks prior to the first dose of TL32711. Subjects must be well recovered from acute effects of surgery prior to enrollment.

• Known or suspected diagnosis of human immunodeficiency virus or chronic active Hepatitis B or C.

• Symptomatic or uncontrolled brain metastases requiring current treatment.

• Impaired cardiac function or clinically significant cardiac disease

• QT interval corrected for heart rate (QTcB) >480 msec (including subjects on medication).

• Lack of recovery of prior adverse events to Grade =1 severity (NCI CTCAE v4) (except alopecia) due to therapy administered prior to the initiation of study drug dosing.

• Nursing or pregnant women.

• Known allergy to any of the formulation components of TL32711.

• Any concurrent disease and/or medical condition that in the opinion of the Investigator that would prevent the subject's participation, render the subject at excessive risk (including excessive risks due to the toxicity profile of the planned combination chemotherapeutic regimen), or limit the subject's compliance with the protocol's required evaluations.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• Birinapant

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Center	Detroit	Michigan
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
TetraLogic Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with adverse events as a measure of safety and tolerability	Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters	1 Cycle (3-4 weeks)	Yes
Secondary	Evaluation of anti-tumor efficacy	Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST) and time to progression	Every 2 cycles	No
Secondary	Evaluation of pharmacokinetics and translational biomarkers	Measurement of TL32711 pharmacokinetics: Maximum plasma concentration (Cmax), area under the curve (AUC), half-life (t1/2) and assessment of translational biomarkers in plasma, PBMC's and tumor biopsies. Gene expression profiling of tumor tissue.	Cycle 1 and Cycle 2	No