Gemcitabine Hydrochloride and Smac Mimetic TL32711 in Treating Patients With Advanced Solid Tumors
|Unspecified Adult Solid Tumor, Protocol Specific||Drug: Smac mimetic TL32711 Drug: gemcitabine hydrochloride Other: laboratory biomarker analysis Other: pharmacological study Procedure: biopsy||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of TL32711 In Combination With Gemcitabine in Patients With Advanced Solid Tumors|
- MTD of smac mimetic TL32711 [ Time Frame: During the first course (21 days) ]Defined as the highest dose level at which less than 2 of 6 patients experience study treatment-related dose-limiting toxicity. Summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment.
- Overall toxicity profile characterized by type, frequency, severity (according to the NCI CTCAE version 4.0), timing, seriousness, and relationship to study treatment [ Time Frame: Up to 4 weeks post-treatment ]Summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment.
- Response rates according to the RECIST v1.1 (solid tumor/dose-finding cohort) [ Time Frame: Up to 4 weeks post-treatment ]Data presented in tabular format and summarized descriptively.
- Progression-free survival [ Time Frame: Up to 2 years ]
- Plasma pharmacokinetic parameters of smac mimetic TL32711, gemcitabine hydrochloride and its metabolites [ Time Frame: Days 1 and 8 of course 1 and then day 1 of course 2 (day 22) ]Comparison of pharmacokinetic parameters among the dose levels and drug-drug interaction performed using non-parametric statistical methods for K-independent samples.
|Study Start Date:||April 2012|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive gemcitabine hydrochloride IV over 30 minutes and smac mimetic TL32711 IV over 30 minutes once weekly for 2 weeks. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Smac mimetic TL32711
Other Name: TL32711Drug: gemcitabine hydrochloride
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesProcedure: biopsy
Optional correlative studies
Other Name: biopsies
I. To determine the maximum tolerated dose (MTD) and recommended Phase II dose of TL32711 (smac mimetic TL32711) in combination with gemcitabine (gemcitabine hydrochloride) in patients with advanced solid tumors.
I. To determine the toxicity and safety profile of TL32711 in combination with gemcitabine in patients with advanced solid tumors.
II. To determine the pharmacokinetic profile of TL32711 and gemcitabine when administered in combination.
III. To determine the preliminary efficacy of the study combination in patients with advanced solid tumors.
IV. To determine the relationship between predictive biomarkers and clinical activity using archival tumor tissue samples for biomarker analysis.
OUTLINE: This is a dose-escalation study of smac mimetic TL32711.
Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes and smac mimetic TL32711 IV over 30 minutes once weekly for 2 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for at least 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01573780
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, Pennsylvania|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||Wen Wee Ma||Roswell Park Cancer Institute|