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

NCT ID: NCT01188499

Last Updated: 2016-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2014-03-31

Brief Summary

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

Detailed 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.

Conditions

Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carboplatin/Paclitaxel + Birinapant

Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).

Group Type: EXPERIMENTAL

Birinapant

Intervention Type: DRUG

Irinotecan + Birinapant

Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).

Group Type: EXPERIMENTAL

Birinapant

Intervention Type: DRUG

Docetaxel + Birinapant

Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).

Group Type: EXPERIMENTAL

Birinapant

Intervention Type: DRUG

Gemcitabine + Birinapant

Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle).

Group Type: EXPERIMENTAL

Birinapant

Intervention Type: DRUG

Liposomal Doxorubicin + Birinapant

Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle).

Group Type: EXPERIMENTAL

Birinapant

Intervention Type: DRUG

Interventions

Birinapant

Intervention Type: DRUG

Other Intervention Names

TL32711

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TetraLogic Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John N Nemunaitis, MD

Role: PRINCIPAL_INVESTIGATOR

Mary Crowley Cancer Research Center

Ravi Amaravadi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania, Abramson Cancer Center

Lainie P Martin, MD

Role: PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Alex Adjei, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Patricia LoRusso, DO

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Center

Kyriakos P Papadopoulos, MD

Role: PRINCIPAL_INVESTIGATOR

South Texas Accelerated Research Therapeutics (START)

Zdenka Segota, MD

Role: PRINCIPAL_INVESTIGATOR

Holy Cross Hospital

Locations

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Mary Crowley Cancer Research Center

Dallas, Texas, United States

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, United States

Countries

United States

Other Identifiers

TL32711-POC-0078-PTL

Identifier Type: -

Identifier Source: org_study_id