A Safety, Tolerability and Pharmacokinetic Study of TAS-114 in Combination With Capecitabine in Patients With Advanced Solid Tumors

September 17, 2018 updated by: Taiho Oncology, Inc.

A Phase 1, Open-Label, Non-randomized, Dose-Escalating Safety, Tolerability, and Pharmacokinetic Study of TAS-114 in Combination With Capecitabine in Patients With Advanced Solid Tumors

The purpose of this exploratory study is to investigate the safety and determine the maximum tolerated dose (MTD) of TAS-114 in combination with capecitabine in patients with advanced solid tumors for which the patients have no available therapy likely to convey clinical benefit.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In animal models, co-administration of TAS 114 and capecitabine has shown antitumor effects exceeding the maximum efficacy obtained by capecitabine alone. Developing a novel chemotherapy based on the combined use of TAS-114 and capecitabine may fulfill the need for more efficacious treatment for patients with advanced solid tumors.

The study, evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the TAS-114/ capecitabine regimen in patients with advanced solid tumors, will be conducted in two parts: a Dose-Escalation Phase (Part 1) to determine the MTD; and an Expansion Phase (Part 2) to further evaluate the safety and preliminary efficacy with the MTD.

Study Type

Interventional

Enrollment (Anticipated)

60

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, 90033
        • USC/Norris Comprehensive Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • IU Simon Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute

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. Provided written consent
  2. Is 18 years of age or older

  3. Has histologically or cytologically confirmed advanced, measurable or non-measurable metastatic solid tumors for which the patients have no available therapy to convey clinical benefit Expansion Phase only: The target population should include at least

    1. 12 patients with breast cancer for whom 5 FU chemotherapy is the standard treatment
    2. 28 patients with refractory colorectal cancer.
  4. May have received prior therapies for advanced or metastatic disease
  5. Expansion Phase only: Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009), ie, has at least one measurable lesion
  6. Has ECOG performance status 0 or 1 on Cycle 1, Day 1
  7. Is able to take medications orally
  8. Has adequate organ function as defined by protocol
  9. Women of childl-bearing potential must have a negative pregnancy test within 7 days prior to starting the study drug. Beth males and females must agree to adequate birth control if conception is possible during the study and for 6 months after the last dose
  10. Is willing to and able to comply with scheduled visits and study procedures.

Exclusion Criteria:

  1. Has a known DPD deficiency
  2. Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent, within the specified time frames prior to study drug administration.
  3. Certain serious illnesses or medical conditions
  4. Is receiving concomitant treatment with drugs that may interact with capecitabine
  5. Has had prior gastrectomy
  6. Has known sensitivity to capecitabine or metabolites
  7. Is a pregnant or lactating female

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-114/capecitabine
See intervention description
Drug: TAS-114/capecitabine

Part 1 (dose-escalation phase):

Treatment cycles of TAS-114 and capecitabine orally BID for 14 days followed by 7 days rest until at least one of the discontinuation criteria are met TAS-114 dose starting at 20mg/m2/day with capecitabine dose of 760 mg/m2/day. TAS-114 doses will be escalated for each cohort up to 480mg/m2/day. If MTD is not reached by TAS-114 dose of 480mg/m2/day, the capecitabine dose will be escalated

Part 2 (expansion phase):

TAS-114 and capecitabine MTD established in Part 1 administered BID for 14 days followed by 7-day recovery period (21-day cycle).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The MTD of TAS-114/ capecitabine (defined as the highest dose level at which less than 33% of the patients experience a Dose Limiting Toxicity (DLT) during the first cycle of treatment); DLTs defined by protocol
Time Frame: First cycle of treatment (ie. 21 days)
Only drug-related toxicities during the first cycle are considered in the assessment of DLTs.
First cycle of treatment (ie. 21 days)

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic profiles (peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) of TAS-114, capecitabine and it's metabolite 5-FU)
Time Frame: First cycle of treatment (ie. 21 days)
First cycle of treatment (ie. 21 days)
antitumor activity by tumor assessments according to RECIST criteria
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

Collaborators and Investigators

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

Sponsor

Taiho Oncology, Inc.

Collaborators

Quintiles, 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

November 1, 2012

Primary Completion (Actual)

July 7, 2017

Study Completion (Actual)

July 7, 2017

Study Registration Dates

First Submitted

December 27, 2013

First Submitted That Met QC Criteria

December 30, 2013

First Posted (Estimate)

January 1, 2014

Study Record Updates

Last Update Posted (Actual)

September 18, 2018

Last Update Submitted That Met QC Criteria

September 17, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TPU-TAS-114-101

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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