Advanced Gastrointestinal TumorsPhase 1NCT01916447
A Phase I Study of TAS-102 in Patients With Advanced Gastrointestinal Tumors.
A Phase 1 study testing TAS-102, CPT-11 and Bevacizumab in people with Advanced Gastrointestinal Tumors, run by Taiho Oncology, Inc. at 4 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Gastrointestinal Tumors
- What is being tested?
- TAS-102, CPT-11 and Bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 4 sitesUnited States
- Study dates
- Sep 2013to Sep 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Chicago Clinical Site
Chicago, Illinois, 60611
Los Angeles Clinical Site
Los Angeles, California, 90095
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37212
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
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
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.
Read the 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.
- Conditions
- Advanced Gastrointestinal Tumors
- Being tested
- TAS-102, CPT-11, Bevacizumab
- Keywords
- Angiogenesis Inhibitor, Monoclonal Antibody, Vascular Endothelial Growth Factor A (VEGF-A)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAS-102Drug
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-11Drug
Also called camptothecin-11, irinotecan
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.
BevacizumabDrug
Also called Avastin
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.
| Study group | Role | What they receive |
|---|---|---|
| TAS-102 and CPT-11 with or without Bevacizumab | Experimental | Not described Receives: Drug: TAS-102; Drug: CPT-11; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used.
Measured: 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.
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.
Measured: 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.
Tumor assessments using Response Evlauation Criteria in Solid Tumors (RECIST)
Measured: After every 4 cycles (i.e., every 8 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2013 (estimated)
- Study startSep 2013
- Primary completionSep 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Gastrointestinal TumorsStudies of the same condition, open and under way.
- More trials run by Taiho Oncology, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taiho Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Leonard Saltz, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01916447
- Sponsor's protocol ID
- TPU-TAS-102-109
- Status last verified
- Aug 2024
- First submitted
- 19 Jul 2013
- Last updated
- 5 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01916447
- Acronym / sponsor ID
- TPU-TAS-102-109
- Conditions
- Advanced Gastrointestinal Tumors
- Keywords
- Angiogenesis Inhibitor, Monoclonal Antibody, Vascular Endothelial Growth Factor A (VEGF-A)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Taiho Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2013 (actual)
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 5 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TAS-102 and CPT-11 with or without Bevacizumab | Experimental | Drug: TAS-102, Drug: CPT-11, Drug: Bevacizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAS-102Escalating 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 | TAS-102 and CPT-11 with or without Bevacizumab |
| CPT-11Also: camptothecin-11, irinotecanEscalating 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. | Drug | TAS-102 and CPT-11 with or without Bevacizumab |
| BevacizumabAlso: AvastinDose (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. | Drug | TAS-102 and CPT-11 with or without Bevacizumab |
Primary outcome
Determine maximum tolerated dose
Time frame: Through Cycle 1 and Cycle 2 (ie, 4 weeks)
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.
Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) will be used.
3 secondary outcomes
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
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.
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leonard Saltz, MD principal investigator
Memorial Sloan Kettering Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAS-102, CPT-11 and Bevacizumab in people with Advanced Gastrointestinal Tumors, run by Taiho Oncology, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine maximum tolerated dose (time frame: Through Cycle 1 and Cycle 2 (ie, 4 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2024.