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

Advanced Gastrointestinal Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01916447
• Other study ID #: TPU-TAS-102-109
• Status: Completed
• Phase: Phase 1
• First received: July 19, 2013
• Last updated: October 5, 2017
• Start date: September 2013
• Est. completion date: September 2017

Study information

• Verified date: October 2017
• Source: Taiho Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Gastrointestinal Tumors
• Digestive System Neoplasms
• Gastrointestinal Neoplasms

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Chicago Clinical Site	Chicago	Illinois
United States	Los Angeles Clinical Site	Los Angeles	California
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Taiho Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine maximum tolerated dose	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)
Primary	Safety monitoring including adverse events, vital signs, and laboratory assessments	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	Investigate the safety of TAS-102 and CPT-11 at the MTD administered in combination with Bevacizumab (5 mg/kg IV).	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
Secondary	Investigate the clinical pharmacokinetics (PK) of TAS-102, CPT-11, and their metabolites.	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.
Secondary	Document any preliminary antitumor activity of TAS-102 administered in combination with CPT-11 and in combination with CPT-11 and Bevacizumab.	Tumor assessments using Response Evlauation Criteria in Solid Tumors (RECIST)	After every 4 cycles (i.e., every 8 weeks)