Clinical trial NCT01916447: A Phase I Study of TAS-102 in Patients With Advanced Gastrointestinal Tumors.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Gastrointestinal Tumors
Keywords: Angiogenesis Inhibitor
Monoclonal Antibody
Vascular Endothelial Growth Factor A (VEGF-A)
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2013-08-05
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Determine maximum tolerated dose
timeFrame: Through Cycle 1 and Cycle 2 (ie, 4 weeks)
measure: Safety monitoring including adverse events, vital signs, and laboratory assessments
timeFrame: Safety is assessed through 30 days following last administration of study medication or until initiation of new anticancer treatment.
Secondary outcomes:
measure: Investigate the safety of TAS-102 and CPT-11 at the MTD administered in combination with Bevacizumab (5 mg/kg IV).
timeFrame: Through 30 days following last administration of study medication or until initiation of new anticancer treatment
measure: Investigate the clinical pharmacokinetics (PK) of TAS-102, CPT-11, and their metabolites.
timeFrame: 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.
measure: Document any preliminary antitumor activity of TAS-102 administered in combination with CPT-11 and in combination with CPT-11 and Bevacizumab.
timeFrame: After every 4 cycles (i.e., every 8 weeks)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles Clinical Site
state: California
city: Chicago
country: United States
facility: Chicago Clinical Site
state: Illinois
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Leonard Saltz, MD
role: PRINCIPAL_INVESTIGATOR
References: