Gastro-Intestinal CancerPhase 1NCT01046864
Combination of Brivanib With 5-Fluorouracil/Leucovorin (5FU/LV) and 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI)
A Phase 1 study testing 5-FU, Leucovorin and Irinotecan in people with Gastro-Intestinal Cancer, run by Bristol-Myers Squibb at 6 sites in 3 countries.
Trial summary
The purpose of this study is to determine a safe and maximum tolerable dose of Brivanib when combined with standard dose 5FU/LV and FOLFIRI. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Gastro-Intestinal Cancer
- What is being tested?
- 5-FU, Leucovorin and Irinotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 6 sitesin 3 countries
- Study dates
- Feb 2010to Jun 2014
- 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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological/cytological confirmed diagnosis of Gastrointestinal malignancy, except pancreatic cancer
- Eligible for 5FU/LV or FOLFIRI chemotherapy
- ECOG 0-1
- Able to swallow and tolerate tablets
- Life expectancy of 3 months
Who cannot join
- Unwilling to use acceptable method to avoid pregnancy of partner/self for the entire study period and up to 4 weeks after last dose
- Women who are pregnant or breastfeeding
- Pancreatic cancer
- Known brain metastasis, evidence of leptomeningeal disease
- History of thrombo-embolic disease
- Hemorrhage/bleeding events
Show all 17Show fewer
- Uncontrolled or significant cardiovascular disease
- Any 3 or more of the following risk factors: arterial thrombosis , smoking, hypercholesterolemia, hypertension, obesity (BMS>30) and diabetes
- Pre-existing thyroid abnormality, not maintained with medication
- QTC (Fridericia) >450 msec on two consecutive ECG's
- Subjects with concomitant second malignancies ( except adequately treated non-melanoma skin, in situ carcinoma of bladder, cervix or breast, early prostate cancer)
- Any major surgery within 4 weeks of study drug administration
- Increased levels of both D-Dimer and Prothrombin fragment 1 +2
- Arm B and C only-positive UGT1A1 genotype of TA7/TA7
- History of allergy of brivanib or drug class
- History of severe reactions to fluoropyrimidine therapy or irinotecan
- Prior therapy with brivanib
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States3 sites
Texas Oncology
Dallas, Texas, 75246
Usc/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Scott & White Memorial Hospital And Clinic
Temple, Texas, 76508
Canada2 sites
Local Institution
Edmonton, Alberta, T6G 1Z2
Local Institution
Ottawa, Ontario, K1H 8L6
About this study
Official title: A Phase Ib Multiple Ascending Dose Study to Evaluate the Safety of Brivanib in Combination With 5-Fluorouracil/Leucovorin (5FU/LV) and Brivanib in Combination With 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI) in Subjects With Advanced or Metastatic Gastrointestinal Malignancies
The purpose of this study is to determine a safe and maximum tolerable dose of Brivanib when combined with standard dose 5FU/LV and FOLFIRI.
- Conditions
- Gastro-Intestinal Cancer
- Being tested
- 5-FU, Leucovorin, Irinotecan, Brivanib
- Keywords
- Gastro-Intestinal Cancer, NOS
- Medical subject headings
- Pyloric Stenosis, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FUDrug
Also called Fluorouracil
IV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity
LeucovorinDrug
Also called Folinic acid
IV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
5-FUDrug
Also called Fluorouracil
IV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity
IrinotecanDrug
Also called Camptosar
IV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
BrivanibDrug
Tablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity
BrivanibDrug
Also called BMS-582664
Tablets, Oral, 600 - 800 mg, once daily, Until disease progression/toxicity
BrivanibDrug
Also called BMS-582664
Tablets, Oral, 800 mg, once daily, Until disease progression/toxicity
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Drug: 5-FU; Drug: Leucovorin; Drug: Brivanib |
| Arm 2 | Experimental | Not described Receives: Drug: 5-FU; Drug: Leucovorin; Drug: Irinotecan; Drug: Brivanib |
| Arm 3 | Experimental | Japanese Population Receives: Drug: 5-FU; Drug: Leucovorin; Drug: Irinotecan; Drug: Brivanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety-Toxicity, evaluated according to NCI Common Terminology Criteria for Adverse Events v3.0. Assessments based on medical review of adverse events, results of vital signs, ECGs, echocardiography, physical examinations, and clinical laboratory tests
Measured: Cycle 4, Day 1
Secondary outcomes (3)
Pharmacokinetics (Cmax, Tmax, AUC (TAU), T-HALF) plasma concentration vs time for brivanib given alone and in combination with FOLFIRI. Individual concentrations (C) of 5FU will be calculated from samples on Day 2 in the presence and absence of Brivanib
Measured: Cycle 2, Day 2
Efficacy-Tumor BOR determined for treated subjects by radiological responses assessed by CT scan or MRI, by RECIST criteria (v1.1). Radiological tumor assessments to evaluate response & progression will be done every 8 wks or more frequently if indicated
Measured: Every 8 weeks
Exploratory Measures (Biomarkers for Predictive Analysis): Potential predictive markers, including activity of FGF, VEGF and related pathways as well as K-RAS mutation status, will be evaluated based on blood or tumor samples
Measured: Cycle 1, Cycle 2, every other cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2010 (estimated)
- Study startFeb 2010
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastro-Intestinal CancerStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe 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
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01046864
- Sponsor's protocol ID
- CA182-046
- Other IDs
- 2009-016699-63, 2009
- Status last verified
- Sep 2014
- First submitted
- 11 Jan 2010
- Last updated
- 16 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Multiple Ascending Dose Study to Evaluate the Safety of Brivanib in Combination With 5-Fluorouracil/Leucovorin (5FU/LV) and Brivanib in Combination With 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI) in Subjects With Advanced or Metastatic Gastrointestinal Malignancies
- ClinicalTrials.gov ID
- NCT01046864
- Acronym / sponsor ID
- CA182-046
- Conditions
- Gastro-Intestinal Cancer
- Keywords
- Gastro-Intestinal Cancer, NOS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Feb 2010
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 12 Jan 2010 (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 determine a safe and maximum tolerable dose of Brivanib when combined with standard dose 5FU/LV and FOLFIRI.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: 5-FU, Drug: Leucovorin, Drug: Brivanib |
| Arm 2 | Experimental | Drug: 5-FU, Drug: Leucovorin, Drug: Irinotecan, Drug: Brivanib |
| Arm 3 | Experimental | Drug: 5-FU, Drug: Leucovorin, Drug: Irinotecan, Drug: BrivanibJapanese Population |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histological/cytological confirmed diagnosis of Gastrointestinal malignancy, except pancreatic cancer
- Eligible for 5FU/LV or FOLFIRI chemotherapy
- ECOG 0-1
- Able to swallow and tolerate tablets
- Life expectancy of 3 months
Key exclusion criteria (17 listed)
- Unwilling to use acceptable method to avoid pregnancy of partner/self for the entire study period and up to 4 weeks after last dose
- Women who are pregnant or breastfeeding
- Pancreatic cancer
- Known brain metastasis, evidence of leptomeningeal disease
- History of thrombo-embolic disease
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 |
|---|---|---|
| 5-FUAlso: FluorouracilIV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity | Drug | Arm 1, Arm 2, Arm 3 |
| LeucovorinAlso: Folinic acidIV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity | Drug | Arm 1, Arm 2, Arm 3 |
| 5-FUAlso: FluorouracilIV solution, IV infusion over 46 hours, 2400 mg/m², Every 14 days, Until disease progression/toxicity | Drug | Arm 1, Arm 2, Arm 3 |
| IrinotecanAlso: CamptosarIV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity | Drug | Arm 2, Arm 3 |
| BrivanibTablets, Oral, 400 - 800 mg, once daily, Until disease progression/toxicity | Drug | Arm 1 |
| BrivanibAlso: BMS-582664Tablets, Oral, 600 - 800 mg, once daily, Until disease progression/toxicity | Drug | Arm 2 |
| BrivanibAlso: BMS-582664Tablets, Oral, 800 mg, once daily, Until disease progression/toxicity | Drug | Arm 3 |
Primary outcome
Safety-Toxicity, evaluated according to NCI Common Terminology Criteria for Adverse Events v3.0. Assessments based on medical review of adverse events, results of vital signs, ECGs, echocardiography, physical examinations, and clinical laboratory tests
Time frame: Cycle 4, Day 1
3 secondary outcomes
Pharmacokinetics (Cmax, Tmax, AUC (TAU), T-HALF) plasma concentration vs time for brivanib given alone and in combination with FOLFIRI. Individual concentrations (C) of 5FU will be calculated from samples on Day 2 in the presence and absence of Brivanib
Time frame: Cycle 2, Day 2
Efficacy-Tumor BOR determined for treated subjects by radiological responses assessed by CT scan or MRI, by RECIST criteria (v1.1). Radiological tumor assessments to evaluate response & progression will be done every 8 wks or more frequently if indicated
Time frame: Every 8 weeks
Exploratory Measures (Biomarkers for Predictive Analysis): Potential predictive markers, including activity of FGF, VEGF and related pathways as well as K-RAS mutation status, will be evaluated based on blood or tumor samples
Time frame: Cycle 1, Cycle 2, every other cycle
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 16 Sep 2014.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 5-FU, Leucovorin and Irinotecan in people with Gastro-Intestinal Cancer, run by Bristol-Myers Squibb at 6 sites in 3 countries.
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 5 inclusion and 17 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 16 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Canada, France. 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?
Safety-Toxicity, evaluated according to NCI Common Terminology Criteria for Adverse Events v3.0. Assessments based on medical review of adverse events, results of vital signs, ECGs, echocardiography, physical examinations, and clinical laboratory tests (time frame: Cycle 4, Day 1). 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 16 Sep 2014.