Study of the Safety of Escalating Doses of TAS-102 in Combination With CPT-11 in Patients With Advanced Gastrointestinal Tumors

This study is currently recruiting participants.
Verified September 2013 by Taiho Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Taiho Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT01916447
First received: July 19, 2013
Last updated: September 16, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Advanced Gastrointestinal Tumors
Drug: TAS-102
Drug: CPT-11
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 in Patients With Advanced Gastrointestinal Tumors

Resource links provided by NLM:


Further study details as provided by Taiho Oncology, Inc.:

Primary Outcome Measures:
  • Determine maximum tolerated dose [ Time Frame: Through Cycle 1 and Cycle 2 (ie, 4 weeks) ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used.


Secondary Outcome Measures:
  • Maximum observed plasma concentration (Cmax) 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 after administration of TAS 102 in combination with CPT 11 ] [ Designated as safety issue: No ]
  • Time to maximum plasma concentration (Tmax) 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 after administration of TAS 102 in combination with CPT 11 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to the last measurable plasma concentration (AUC0-last) 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 after administration of TAS 102 in combination with CPT 11 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) 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 after administration of TAS 102 in combination with CPT 11 ] [ Designated as safety issue: No ]
  • Apparent terminal phase elimination half-life (t½) 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 after administration of TAS 102 in combination with CPT 11 ] [ Designated as safety issue: No ]
  • Clearance (CL/F) of TAS-102 [ 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 after administration of TAS 102 in combination with CPT 11 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution (Vd/F) of TAS-102 [ 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 after administration of TAS 102 in combination with CPT 11 ] [ Designated as safety issue: No ]
  • Tumor assessments using Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: After every 4 cycles (ie, every 8 weeks) through Cycle 24 (ie, 48 weeks) or as clinically necessary. ] [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: September 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAS-102 and CPT-11 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 Name: camptothecin-11, irinotecan

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Has advanced gastrointestinal tumors refractory to at least 1 chemotherapy and for which no curative therapy exists
  2. Has a malignancy of gastrointestinal origin or adenocarcinoma of unknown primary, likely to be of GI origin
  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. Certain serious illnesses or medical condition(s)
  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, or their components
  5. Is a pregnant or lactating female
  6. Refuses to use an adequate means of contraception (including male patients)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01916447

Contacts
Contact: Manuel Aivado, MD, PhD 855-598-8259 aivado@taihopui.com

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Leonard Saltz, MD    646-888-4181    saltzl@mskcc.org   
Principal Investigator: Leonard Saltz, MD         
Sponsors and Collaborators
Taiho Oncology, Inc.
Investigators
Principal Investigator: Leonard Saltz, MD Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: Taiho Oncology, Inc.
ClinicalTrials.gov Identifier: NCT01916447     History of Changes
Other Study ID Numbers: TPU-TAS-102-109
Study First Received: July 19, 2013
Last Updated: September 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Taiho Oncology, Inc.:
Advanced gastrointestinal tumors refractory to at least 1 chemotherapy and for which no curative therapy exists

Additional relevant MeSH terms:
Digestive System Neoplasms
Gastrointestinal Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Camptothecin
Irinotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2014