Biliary Tract Cancer, Gallbladder Adenocarcinoma
Conditions
Keywords
Avastin, GEMOX
Brief summary
The purposes of this study are to test the safety of bevacizumab when given in combination with gemcitabine and oxaliplatin and to see what effects (good and bad) this combination has on patients with cancer of bile duct or gallbladder. Bevacizumab has been shown to slow or stop cell growth in tumors by decreasing the blood supply to the tumors.
Detailed description
* The chemotherapy drugs are given twice every 28 days. This 28 day period is called a cycle of study treatment. * Bevacizumab will be administered by IV over 90 minutes on day 1 and day 15. Gemcitabine will be administered by IV over 1 hour and 40 minutes on days 1 and 15 of each cycle. Oxaliplatin will be administered by IV for 2 hours on days 1 and 15 of each cycle. * The following tests and procedures will be performed on day 1 and day 15 or each cycle: physical examination; medical history; blood work; and urine test. A PET scan will be repeated at the end of cycle 2 and CT scans will be repeated once every 8 weeks. * Participants will continue to receive cycles of study treatment as long as their disease does not progress and they are not experiencing any serious side effects.
Interventions
DRUGBevacizumab
Given intravenously on days 1 and 15 of each 28-day cycle. Participants may continue to receive study treatment as lond as their disease does not progress and they do not experience any serious side effects.
DRUGGemcitabine
Given intravenously on days 1 and 15 of each 28-day cycle. Participants may continue to receive study treatment as lond as their disease does not progress and they do not experience any serious side effects.
DRUGOxaliplatin
Given intravenously on days 1 and 15 of each 28-day cycle. Participants may continue to receive study treatment as lond as their disease does not progress and they do not experience any serious side effects.
Sponsors
Genentech, Inc.
Sanofi
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed, locally unresectable or metastatic biliary tract or gallbladder adenocarcinoma. Patients must have at least one measurable lesion outside prior radiation field. * Zero to one prior chemotherapy for biliary tract or gallbladder cancer * Age \> 18 years * ECOG performance status 0-2 * Life expectancy \> 12 weeks * Adequate organ and bone marrow function
Exclusion criteria
* Chemotherapy within past 3 weeks of initiation of therapy * Pregnant or lactating women * Clinically apparent central nervous system metastases or carcinomatous meningitis * Biliary obstruction with inadequate drainage and total bilirubin \> 2.5 mg/dL * Concurrent malignancy of any site, except limited basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix * Uncontrolled serious medical or psychiatric illness * Pre-existing peripheral neuropathy of grade 2 or greater severity according to the Common Terminology Criteria of the NCI (version 3.0) * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study * Blood pressure of \> 150/100 mmHg * Unstable angina * NYHA Grade II or greater congestive heart failure * History of myocardial infarction or stroke within 6 months * Clinically significant peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Major surgical procedure, open biopsy, or significant traumatic injury with 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 * Serious, non-healing wound, ulcer, or bone fracture
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival | 2 years | To assess the median progression free survival in patients with BTC on GEMOX-B. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. In addition, death in the absence of radiological disease progression was also categorized as progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 2 years | To assess the overall response rate of GEMOX-B in patients with advanced BTC. Response rate is determined through Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab, Gemcitabine, Oxaliplatin * The chemotherapy drugs are given twice every 28 days. This 28 day period is called a cycle of study treatment.
* Bevacizumab will be administered by IV over 90 minutes on day 1 and day 15. Gemcitabine will be administered by IV over 1 hour and 40 minutes on days 1 and 15 of each cycle. Oxaliplatin will be administered by IV for 2 hours on days 1 and 15 of each cycle.
* Participants will continue to receive cycles of study treatment as long as their disease does not progress and they are not experiencing any serious side effects.
Bevacizumab: Given intravenously on days 1 and 15 of each 28-day cycle. Participants may continue to receive study treatment as lond as their disease does not progress and they do not experience any serious side effects.
Gemcitabine: Given intravenously on days 1 and 15 of each 28-day cycle. Participants may continue to receive study treatment as lond as their disease does not progress and they do not experience any serious side effects. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Radiographic disease progression | 16 |
| Overall Study | Symptomatic deterioration | 5 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Bevacizumab, Gemcitabine, Oxaliplatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Age, Continuous | 60 years |
| Gender Female | 14 Participants |
| Gender Male | 21 Participants |
| Region of Enrollment United States | 35 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 35 |
| serious Total, serious adverse events | 12 / 35 |
Outcome results
Primary
Median Progression Free Survival
To assess the median progression free survival in patients with BTC on GEMOX-B. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. In addition, death in the absence of radiological disease progression was also categorized as progression.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab, Gemcitabine, Oxaliplatin | Median Progression Free Survival | 7.0 months |
p-value: <0.05Kaplan-Meier
Secondary
Overall Response Rate
To assess the overall response rate of GEMOX-B in patients with advanced BTC. Response rate is determined through Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab, Gemcitabine, Oxaliplatin | Overall Response Rate | 0 percentage of participants |
p-value: 0.05Kaplan-Meier