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

NCT01916447 | Completed Phase 1

• 1 other identifier: TPU-TAS-102-109
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 4

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.

Conditions

Advanced Gastrointestinal Tumors

Keywords

Angiogenesis Inhibitor; Monoclonal Antibody; Vascular Endothelial Growth Factor A (VEGF-A)

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (3)

• Investigate the safety of TAS-102 and CPT-11 at the MTD administered in combination with Bevacizumab (5 mg/kg IV).

  Through 30 days following last administration of study medication or until initiation of new anticancer treatment

• Investigate the clinical pharmacokinetics (PK) of TAS-102, CPT-11, and their metabolites.

  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.

• Document any preliminary antitumor activity of TAS-102 administered in combination with CPT-11 and in combination with CPT-11 and Bevacizumab.

  After every 4 cycles (i.e., every 8 weeks)

Study Arms (1)

TAS-102 and CPT-11 with or without Bevacizumab

EXPERIMENTAL

Drug: TAS-102; Drug: CPT-11; Drug: Bevacizumab

Interventions

TAS-102 DRUG

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.

TAS-102 and CPT-11 with or without Bevacizumab

CPT-11 DRUG

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.

Also known as: camptothecin-11, irinotecan

TAS-102 and CPT-11 with or without Bevacizumab

Bevacizumab DRUG

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.

Also known as: Avastin

TAS-102 and CPT-11 with or without Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has provided written informed consent
• Has advanced gastrointestinal tumors refractory to at least 1 chemotherapy
• ECOG performance status of 0 or 1
• Is able to take medications orally
• Has adequate organ function (bone marrow, kidney and liver)
• 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.

You may not qualify if:

• 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
• Presence of serious illnesses or medical condition(s) e.g. brain metastases, systemic infection, heart failure
• Has unresolved toxicity of greater than or equal to CTCAE Grade 1 attributed to any prior therapies
• Known sensitivity to TAS-102, CPT-11, Bevacizumab, or their components
• Is a pregnant or lactating female
• Has had either partial or total gastrectomy

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (4)

Los Angeles Clinical Site

Los Angeles, California, 90095, United States

Location

Chicago Clinical Site

Chicago, Illinois, 60611, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37212, United States

Location

MeSH Terms

Interventions

trifluridine tipiracil drug combination; Irinotecan; Bevacizumab

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Leonard Saltz, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2013
• First Posted: August 5, 2013
• Study Start: September 1, 2013
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: September 5, 2024

Record last verified: 2024-08

Locations

US (4)