Back to resultsA Phase I Study of TAS-102 in Patients With Advanced Gastrointestinal Tumors.
Primary Purpose
Advanced Gastrointestinal Tumors
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TAS-102
CPT-11
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Gastrointestinal Tumors focused on measuring Angiogenesis Inhibitor, Monoclonal Antibody, Vascular Endothelial Growth Factor A (VEGF-A)
Eligibility Criteria
Inclusion Criteria:
- Has provided written informed consent
- Has advanced gastrointestinal tumors refractory to at least 1 chemotherapy
- ECOG performance status of 0 or 1
- Is able to take medications orally
- Has adequate organ function (bone marrow, kidney and liver)
- Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.
Exclusion Criteria:
- Has had certain other recent treatment e.g. major surgery, extended field radiation, anticancer therapy, received investigational agent, within the specified time frames prior to study drug administration
- Presence of serious illnesses or medical condition(s) e.g. brain metastases, systemic infection, heart failure
- Has unresolved toxicity of greater than or equal to CTCAE Grade 1 attributed to any prior therapies
- Known sensitivity to TAS-102, CPT-11, Bevacizumab, or their components
- Is a pregnant or lactating female
- Has had either partial or total gastrectomy
Sites / Locations
- Los Angeles Clinical Site
- Chicago Clinical Site
- Memorial Sloan-Kettering Cancer Center
- Vanderbilt Ingram Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TAS-102 and CPT-11 with or without Bevacizumab
Arm Description
Outcomes
Primary Outcome Measures
Determine maximum tolerated dose
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
Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used.
Secondary Outcome Measures
Investigate the safety of TAS-102 and CPT-11 at the MTD administered in combination with Bevacizumab (5 mg/kg IV).
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.
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.
Tumor assessments using Response Evlauation Criteria in Solid Tumors (RECIST)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01916447
Brief Title
A Phase I Study of TAS-102 in Patients With Advanced Gastrointestinal Tumors.
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
September 2013 (Actual)
Primary Completion Date
September 2017 (Actual)
Study Completion Date
September 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Taiho Oncology, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to investigate the safety and determine the maximum tolerated dose of TAS-102 administered in combination with CPT-11 in patients with advanced gastrointestinal tumors.
Detailed Description
This is an open-label, non-randomized, dose-escalation, Phase 1 study of TAS-102 administered in combination with CPT-11. The study will be conducted in 2 parts: a Dose Escalation Phase (Part 1) to determine the maximum tolerated dose and an Expansion Phase (Part 2) to further evaluate the safety, pharmacokinetics, and preliminary efficacy of the maximum tolerated dose. Patients will be assigned to sequential dose-level cohorts with each cohort corresponding to a pre-specified dose of TAS-102 and CPT-11 combination. Escalation to the subsequent dose level will occur only after the previous dose level is determined to be safe.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Gastrointestinal Tumors
Keywords
Angiogenesis Inhibitor, Monoclonal Antibody, Vascular Endothelial Growth Factor A (VEGF-A)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TAS-102 and CPT-11 with or without Bevacizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
TAS-102
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
CPT-11
Other Intervention Name(s)
camptothecin-11, irinotecan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Determine maximum tolerated dose
Description
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.
Time Frame
Through Cycle 1 and Cycle 2 (ie, 4 weeks)
Title
Safety monitoring including adverse events, vital signs, and laboratory assessments
Description
Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used.
Time Frame
Safety is assessed through 30 days following last administration of study medication or until initiation of new anticancer treatment.
Secondary Outcome Measure Information:
Title
Investigate the safety of TAS-102 and CPT-11 at the MTD administered in combination with Bevacizumab (5 mg/kg IV).
Description
Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used.
Time Frame
Through 30 days following last administration of study medication or until initiation of new anticancer treatment
Title
Investigate the clinical pharmacokinetics (PK) of TAS-102, CPT-11, and their metabolites.
Description
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.
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.
Title
Document any preliminary antitumor activity of TAS-102 administered in combination with CPT-11 and in combination with CPT-11 and Bevacizumab.
Description
Tumor assessments using Response Evlauation Criteria in Solid Tumors (RECIST)
Time Frame
After every 4 cycles (i.e., every 8 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has provided written informed consent
Has advanced gastrointestinal tumors refractory to at least 1 chemotherapy
ECOG performance status of 0 or 1
Is able to take medications orally
Has adequate organ function (bone marrow, kidney and liver)
Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.
Exclusion Criteria:
Has had certain other recent treatment e.g. major surgery, extended field radiation, anticancer therapy, received investigational agent, within the specified time frames prior to study drug administration
Presence of serious illnesses or medical condition(s) e.g. brain metastases, systemic infection, heart failure
Has unresolved toxicity of greater than or equal to CTCAE Grade 1 attributed to any prior therapies
Known sensitivity to TAS-102, CPT-11, Bevacizumab, or their components
Is a pregnant or lactating female
Has had either partial or total gastrectomy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leonard Saltz, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Los Angeles Clinical Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Chicago Clinical Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Vanderbilt Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase I Study of TAS-102 in Patients With Advanced Gastrointestinal Tumors.
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