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

October 5, 2017 updated by: Taiho Oncology, Inc.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

65

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Los Angeles Clinical Site
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Chicago Clinical Site
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt Ingram Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Through Cycle 1 and Cycle 2 (ie, 4 weeks)
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.
Safety is assessed through 30 days following last administration of study medication or until initiation of new anticancer treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Through 30 days following last administration of study medication or until initiation of new anticancer treatment
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.
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.
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)
After every 4 cycles (i.e., every 8 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taiho Oncology, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2013

Primary Completion (Actual)

September 1, 2017

Study Completion (Actual)

September 1, 2017

Study Registration Dates

First Submitted

July 19, 2013

First Submitted That Met QC Criteria

August 2, 2013

First Posted (Estimate)

August 5, 2013

Study Record Updates

Last Update Posted (Actual)

October 6, 2017

Last Update Submitted That Met QC Criteria

October 5, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TPU-TAS-102-109

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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