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

Tracking Information
First Submitted Date ICMJE	August 23, 2010
First Posted Date ICMJE	August 25, 2010
Results First Submitted Date	April 21, 2016
Results First Posted Date	May 30, 2016
Last Update Posted Date	May 30, 2016
Study Start Date ICMJE	October 2010
Actual Primary Completion Date	October 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 23, 2010)	Number of Subjects With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 1 Cycle (3-4 weeks) ]; Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01188499 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 12, 2011)	Evaluation of Anti-tumor Efficacy [ Time Frame: Every 2 cycles ]Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST) and time to progression; Evaluation of Pharmacokinetics and Translational Biomarkers [ Time Frame: Cycle 1 and Cycle 2 ]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.
Original Secondary Outcome Measures ICMJE; (submitted: August 23, 2010)	Evaluation of Anti-tumor Efficacy [ Time Frame: Every 2 cycles ]Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST); Evaluation of Pharmacokinetics and Translational Biomarkers [ Time Frame: Cycle 1 and Cycle 2 ]Measurement of TL32711 pharmacokinetics (Cmax, AUC, t1/2) and assessment of translational biomarkers in plasma and blood
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Dose Escalation, Combination Chemotherapy Safety Study of Birinapant (TL32711), in Subjects With Advanced or Metastatic Solid Tumors
Official Title ICMJE	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
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Cancer
Intervention ICMJE	Drug: Birinapant; Other Name: TL32711
Study Arms	Experimental: 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). Intervention: Drug: Birinapant; Experimental: 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). Intervention: Drug: Birinapant; Experimental: 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). Intervention: Drug: Birinapant; Experimental: 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). Intervention: Drug: Birinapant; Experimental: 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). Intervention: Drug: Birinapant
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 1, 2016)	176
Original Estimated Enrollment ICMJE; (submitted: August 23, 2010)	120
Actual Study Completion Date	March 2014
Actual Primary Completion Date	October 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01188499
Other Study ID Numbers ICMJE	TL32711-POC-0078-PTL
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	TetraLogic Pharmaceuticals
Study Sponsor ICMJE	TetraLogic Pharmaceuticals
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: 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
PRS Account	TetraLogic Pharmaceuticals
Verification Date	April 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP