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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by Taiho Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Taiho Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT01916447
First received: July 19, 2013
Last updated: July 29, 2015
Last verified: July 2015
  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
Drug: Bevacizumab
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 and Bevacizumab 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:
  • 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 ] [ 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.

  • 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. ] [ Designated as safety issue: No ]
    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. [ Time Frame: After every 4 cycles (i.e., every 8 weeks) ] [ Designated as safety issue: No ]
    Tumor assessments using Response Evlauation Criteria in Solid Tumors (RECIST)


Estimated Enrollment: 78
Study Start Date: September 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Avastin

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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01916447

Contacts
Contact: Jabed Seraj, MD, PhD 855-598-8259 seraj@taihopui.com

Locations
United States, California
Los Angeles Clinical Site Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Jabed Seraj, MD, PhD.    855-598-8259    seraj@taihopui.com   
United States, Illinois
Chicago Clinical Site Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Jabed Seraj, MD, PhD.    855-598-8259    seraj@taihopui.com   
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         
United States, Tennessee
Vanderbilt Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37212
Contact: Jabed Seraj, MD, PhD    855-598-8259    seraj@taihopui.com   
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: July 29, 2015
Health Authority: United States: Food and Drug Administration

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
Digestive System Diseases
Gastrointestinal Diseases
Neoplasms
Neoplasms by Site
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on September 01, 2015