A Phase I Study of TAS-102 in Patients With Advanced Gastrointestinal Tumors.
|ClinicalTrials.gov Identifier: NCT01916447|
Recruitment Status : Completed
First Posted : August 5, 2013
Last Update Posted : October 6, 2017
|Condition or disease||Intervention/treatment||Phase|
|Advanced Gastrointestinal Tumors||Drug: TAS-102 Drug: CPT-11 Drug: Bevacizumab||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||65 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1, Open-label, Non-randomized, Dose-escalating Safety, Tolerability, and Pharmacokinetic Study of TAS-102 in Combination With CPT-11 and Bevacizumab in Patients With Advanced Gastrointestinal Tumors|
|Actual Study Start Date :||September 2013|
|Actual Primary Completion Date :||September 2017|
|Actual Study Completion Date :||September 2017|
|Experimental: TAS-102 and CPT-11 with or without Bevacizumab||
Escalating doses (20-35 mg/m2/dose, based on tolerability), orally, twice daily on days 1-5 of each 14-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.Drug: CPT-11
Escalating doses (30-minute infusion of 120-180 mg/m2/dose, based on tolerability), IV (in the vein) on Day 1 of each 14-day treatment cycle. Number of cycles: until at least one of the discontinuation criteria is met.
Other Name: camptothecin-11, irinotecanDrug: Bevacizumab
Dose (infusion of 5 mg/kg administered per site standard practice), IV (in the vein) on Day 1 of each 14-day treatment cycle. Number of cycles: until at least one of the discontinuation criteria is met.
Other Name: Avastin
- Determine maximum tolerated dose [ Time Frame: Through Cycle 1 and Cycle 2 (ie, 4 weeks) ]The maximum tolerated dose is defined as the highest dose level at which less than 33% of the evaluable patients treated experience a dose-limiting toxicity during Cycle 1 or Cycle 2 (ie, during the first 4 weeks) of study drug administration.
- Safety monitoring including adverse events, vital signs, and laboratory assessments [ Time Frame: Safety is assessed through 30 days following last administration of study medication or until initiation of new anticancer treatment. ]Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used.
- Investigate the safety of TAS-102 and CPT-11 at the MTD administered in combination with Bevacizumab (5 mg/kg IV). [ Time Frame: Through 30 days following last administration of study medication or until initiation of new anticancer treatment ]Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used.
- Investigate the clinical pharmacokinetics (PK) of TAS-102, CPT-11, and their metabolites. [ Time Frame: Blood samples will be collected in Cycle 1 at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24 and 48 hours post AM dose of TAS-102 in combination with CPT-11. ]PK analysis for FTD, FTY, TPI, CPT-11, and SN-38 in plasma and will include Cmax, Tmax, AUC0-last, AUC0-inf, and T1/2. FTD and TPI: CL/F, Vd/F will be calculated.
- Document any preliminary antitumor activity of TAS-102 administered in combination with CPT-11 and in combination with CPT-11 and Bevacizumab. [ Time Frame: After every 4 cycles (i.e., every 8 weeks) ]Tumor assessments using Response Evlauation Criteria in Solid Tumors (RECIST)
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01916447
|United States, California|
|Los Angeles Clinical Site|
|Los Angeles, California, United States, 90095|
|United States, Illinois|
|Chicago Clinical Site|
|Chicago, Illinois, United States, 60611|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Tennessee|
|Vanderbilt Ingram Cancer Center|
|Nashville, Tennessee, United States, 37212|
|Principal Investigator:||Leonard Saltz, MD||Memorial Sloan Kettering Cancer Center|