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

NCT01188499 | Completed Phase 1 Results

• 1 other identifier: TL32711-POC-0078-PTL
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Cancer

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (2)

• Evaluation of Anti-tumor Efficacy

  Every 2 cycles

• Evaluation of Pharmacokinetics and Translational Biomarkers

  Cycle 1 and Cycle 2

Study Arms (5)

Carboplatin/Paclitaxel + Birinapant

EXPERIMENTAL

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).

Drug: Birinapant

Irinotecan + Birinapant

EXPERIMENTAL

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).

Drug: Birinapant

Docetaxel + Birinapant

EXPERIMENTAL

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).

Drug: Birinapant

Gemcitabine + Birinapant

EXPERIMENTAL

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).

Drug: Birinapant

Liposomal Doxorubicin + Birinapant

EXPERIMENTAL

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).

Drug: Birinapant

Interventions

Birinapant DRUG

Also known as: TL32711

Carboplatin/Paclitaxel + Birinapant; Docetaxel + Birinapant; Gemcitabine + Birinapant; Irinotecan + Birinapant; Liposomal Doxorubicin + Birinapant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• TetraLogic Pharmaceuticals: lead

Study Sites (7)

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75201, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

birinapant

Results Point of Contact

• Title: Vice President, Clinical Research
• Organization: TetraLogic Pharmaceuticals

Jeffrey.Skolnik@tetralogicpharma.com

610-889-9900

Study Officials

• John N Nemunaitis, MD

  Mary Crowley Cancer Research Center

  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

  PRINCIPAL INVESTIGATOR

• Patricia LoRusso, DO

  Barbara Ann Karmanos Cancer Center

  PRINCIPAL INVESTIGATOR

• Kyriakos P Papadopoulos, MD

  South Texas Accelerated Research Therapeutics (START)

  PRINCIPAL INVESTIGATOR

• Zdenka Segota, MD

  Holy Cross Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2010
• First Posted: August 25, 2010
• Study Start: October 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: March 1, 2014
• Last Updated: May 30, 2016
• Results First Posted: May 30, 2016

Record last verified: 2016-04

Locations

US (7)