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A Phase I Study of TAS-102 in Patients With Advanced Gastrointestinal Tumors.

Sponsor
Taiho Oncology, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01916447
Collaborator
(none)
65
Enrollment
4
Locations
1
Arm
48
Actual Duration (Months)
16.3
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
65 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 :
Sep 1, 2013
Actual Primary Completion Date :
Sep 1, 2017
Actual Study Completion Date :
Sep 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: TAS-102 and CPT-11 with or without Bevacizumab

Drug: TAS-102
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 Names:
  • camptothecin-11, irinotecan

    • Drug: 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 Names:
  • Avastin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Determine maximum tolerated dose [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.

    2. Safety monitoring including adverse events, vital signs, and laboratory assessments [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.

    Secondary Outcome Measures

    1. Investigate the safety of TAS-102 and CPT-11 at the MTD administered in combination with Bevacizumab (5 mg/kg IV). [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.

    2. Investigate the clinical pharmacokinetics (PK) of TAS-102, CPT-11, and their metabolites. [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.

    3. Document any preliminary antitumor activity of TAS-102 administered in combination with CPT-11 and in combination with CPT-11 and Bevacizumab. [After every 4 cycles (i.e., every 8 weeks)]

      Tumor assessments using Response Evlauation Criteria in Solid Tumors (RECIST)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Has provided written informed consent

    2. Has advanced gastrointestinal tumors refractory to at least 1 chemotherapy

    3. ECOG performance status of 0 or 1

    4. Is able to take medications orally

    5. Has adequate organ function (bone marrow, kidney and liver)

    6. 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:

    1. 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

    2. Presence of serious illnesses or medical condition(s) e.g. brain metastases, systemic infection, heart failure

    3. Has unresolved toxicity of greater than or equal to CTCAE Grade 1 attributed to any prior therapies

    4. Known sensitivity to TAS-102, CPT-11, Bevacizumab, or their components

    5. Is a pregnant or lactating female

    6. Has had either partial or total gastrectomy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Los Angeles Clinical Site Los Angeles California United States 90095
    2 Chicago Clinical Site Chicago Illinois United States 60611
    3 Memorial Sloan-Kettering Cancer Center New York New York United States 10065
    4 Vanderbilt Ingram Cancer Center Nashville Tennessee United States 37212

    Sponsors and Collaborators

    • Taiho Oncology, Inc.

    Investigators

    • Principal Investigator: Leonard Saltz, MD, Memorial Sloan Kettering Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Taiho Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT01916447
    Other Study ID Numbers:
    • TPU-TAS-102-109
    First Posted:
    Aug 5, 2013
    Last Update Posted:
    Oct 6, 2017
    Last Verified:
    Oct 1, 2017
    Keywords provided by Taiho Oncology, Inc.
    Angiogenesis Inhibitor
    Monoclonal Antibody
    Vascular Endothelial Growth Factor A (VEGF-A)
    Additional relevant MeSH terms:
    Digestive System Neoplasms
    Gastrointestinal Neoplasms
    Bevacizumab
    Irinotecan
    Camptothecin

    Study Results

    No Results Posted as of Oct 6, 2017