Biliary Tract Cancer
Conditions
Keywords
Biliary, Oxaliplatin, Bevacizumab
Brief summary
This study is for patients with biliary tract cancer that has spread and who are not candidates for surgical resection. The purpose of this research is to determine if bevacizumab can be safely administered with Modified FOLFOX 6 and find out what effects, good and/or bad, this type of treatment has on biliary cancer. In this study, a combination of chemotherapy, Modified FOLFOX6 and a biologic agent, bevacizumab will be tested. Subjects on this study will receive chemotherapy and bevacizumab every 2 weeks until their disease gets worse or they are unable to tolerate treatment.
Detailed description
This is a single-center, open labeled, single-arm study in patients with previously untreated unresectable biliary tract cancer. This trial will follow a Simon's two-stage optimal design. For the first stage, 9 patients will be accrued. If none of the 9 patients have controlled disease with mFOLFOX6 in combination with bevacizumab, the combination will be rejected and the trial stopped. However, if at least 1 patient of the 9 (11%) respond to treatment in the first stage, then an additional 15 patients will be entered into the second stage, for a total of 24 patients in the phase II study. If 3 (13%) or more patients respond to therapy, then the combination will be considered for further investigation.
Interventions
DRUGBevacizumab in combination with modified FOLFOX6.
Oxaliplatin 85 mg/m2 IV on Day 1 5-FU: 400 mg/m2 IV bolus on Day 1, followed by 2400 mg/M2 over 46 hours Leucovorin: 400 mg IV Day 1 Bevacizumab: 10 mg/kg IV on Day 1 Repeat cycles every 2 weeks until death, disease progression, unacceptable toxicity, patient refusal, or treatment delay \> 4 weeks
Sponsors
Sanofi
Georgetown University
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 or cytologically confirmed diagnosis of non-resectable adenocarcinoma of the biliary tract, including carcinomas of the gallbladder, the intrahepatic or extrahepatic biliary tract, and ampullary cancer * Measurable or evaluable disease * Locally advanced disease that is inoperable ot patients who have had disease recurrence after curative surgical attempt * Ambulatory with an ECOG performance status of 0-1 * Adequate organ and marrow function * Must agree to avoid pregnancy prior to study entry and throughout the duration of study participation * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Any prior chemotherapy * Patients who are receiving other investigational agents * Patients who have received radiotherapy to more than 25% of their bone marrow for any reason * Peripheral neuropathy \>/= 2 * Known brain metastases, uncontrolled seizure disorder, encephalitis * Prior history of hypertensive crisis or hypertensive encephalopathy, uncontrolled hypertension,unstable angina, congestive heart failure of New York Heart Association (NYHA) class 2 or greater, left ventricular ejection fraction less than 50%, clinically significant vascular disease, serious cardiac arrhythmia requiring medication, cardiomyopathy * History of myocardial infarction, unstable angina or stroke/transient ischemic attack (TIA) within 6 months * History of allergy to oxaliplatin, 5-fluoruracil (5-FU), Leucovorin, or Bevacizumab * History of intra-abdominal abscess within 4 weeks of study entry, abdominal fistula, gastrointestinal perforation, active peptic ulcer disease, or inflammatory bowel disease * Evidence of bleeding diathesis or coagulopathy * Serious non-healing wound, ulcer, or bone fracture * Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks of study entry or anticipation of need for major surgery during the course of the study * Minor surgical procedures such as core biopsies within 7 days before enrollment, chemotherapy port placement within 24 hours * Patients on full-dose anticoagulants who have out of range international normalized ratio (INR) or active bleeding * Concurrent malignancy unless the subject has been curatively treated and disease free for \>/= 2 years or the cancer was non-melanoma skin cancer or early cervical cancer * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements * Known HIV or Hepatitis B or C * Life expectancy less than 12 weeks * Pregnant or nursing women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 2 years | Progression-free Survival is defined as the time from randomization (or study initiation) until objective tumor progression or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Toxicity | 8 weeks | The number of patients who underwent FOLFOX dose reductions as a result of Grade 3 toxicity. |
Countries
United States
Participant flow
Recruitment details
9 patients were recruited over the course of the study (2009-2011). All were recruited at Georgetown University Medical Center
Participants by arm
| Arm | Count |
|---|---|
| FOLFOX6 and Bevacizumab Treatment with modified FOLFOX6 and Bevacizumab
Modified FOLFOX6 and Bevacizumab: Oxaliplatin 85 mg/m2 IV on Day 1 5-FU: 400 mg/m2 IV bolus on Day 1, followed by 2400 mg/M2 over 46 hours Leucovorin: 400 mg IV Day 1 Bevacizumab: 10 mg/kg IV on Day 1 Repeat cycles every 2 weeks until death, disease progression, unacceptable toxicity, patient refusal, or treatment delay \> 4 weeks | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | FOLFOX6 and Bevacizumab |
|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 11.7 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 1 / 8 |
Outcome results
Primary
Progression-free Survival
Progression-free Survival is defined as the time from randomization (or study initiation) until objective tumor progression or death.
Time frame: 2 years
Population: Primary outcome of 4 participants out of 8 was undetermined due to several reasons including patient refusal of further follow up.~Of the 4 patients remaining for analysis, progression free survival of 34, 26.3, 7, and 4.7 weeks was seen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFOX6 and Bevacizumab | Progression-free Survival | 16.7 weeks |
Secondary
Safety and Toxicity
The number of patients who underwent FOLFOX dose reductions as a result of Grade 3 toxicity.
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX6 and Bevacizumab | Safety and Toxicity | 3 participants |