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. (see Contacts and Locations)
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

July 19, 2013
September 16, 2013
September 2013
July 2015   (final data collection date for primary outcome measure)
  • 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.
Same as current
Complete list of historical versions of study NCT01916447 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Study of the Safety of Escalating Doses of TAS-102 in Combination With CPT-11 in Patients With Advanced Gastrointestinal Tumors
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

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Advanced Gastrointestinal Tumors
  • 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
Experimental: TAS-102 and CPT-11
Interventions:
  • Drug: TAS-102
  • Drug: CPT-11
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
54
December 2015
July 2015   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact: Manuel Aivado, MD, PhD 855-598-8259 aivado@taihopui.com
United States
 
NCT01916447
TPU-TAS-102-109
No
Taiho Oncology, Inc.
Taiho Oncology, Inc.
Not Provided
Principal Investigator: Leonard Saltz, MD Memorial Sloan-Kettering Cancer Center
Taiho Oncology, Inc.
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP