Study Of Bevacizumab In Combination With 5-FU, Oxaliplatin And External Beam Radiation Followed By Gemcitabine And Bevacizumab For Locally Advanced Pancreatic Cancer

Study Overview

Study of Bevacizumab in Combination With 5-FU, Oxaliplatin and External Beam Radiation Followed by Gemcitabine and Bevacizumab for Locally Advanced Pancreatic Cancer

The purpose of this study is determine the safety of bevacizumab, oxaliplatin, 5-FU, and gemcitabine in combination with external beam radiation therapy(Phase I portion) as well as to begin to collect information about whether this combination treatment is effective in treating patients with locally advanced pancreatic cancer (Phase II portion).

* The combination of all three drugs and radiation treatment has never been given to people before, therefore, we are going to add just one additional drug at a time for safety reasons. * The first group of participants (3-4) who enroll on the study will receive 5-FU, radiation therapy with the added drug oxaliplatin, this is called Regimen level 1. If these participants have few or easily manageable side effects, then another group of participants will be enrolled and will receive 5-FU, radiation, oxaliplatin with the addition of bevacizumab this is called Regimen level 2. * The combination of study drugs and radiation will last about 6 weeks, this 6 week period is called a cycle 1. * Regimen Level 1 will receive the following: oxaliplatin intravenously on days 1, 8, 15, 22, 29, and 36; 5-FU infused by a continuous infusion on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38; radiation therapy Monday-Friday to complete on day 38. * Regimen Level 2 will receive the following; bevacizumab intravenously on days 1, 15, and 29; oxaliplatin intravenously on days 1, 8, 15, 22, 29 and 36; 5-FU infused by continuous infusion days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38; radiation therapy Monday-Friday to complete on day day 38. * The following are tests and procedures that will be performed during cycle 1: physical examination; blood work, urine sample. perfusion CT scan on day 12 (for those participants enrolled at Massachusetts General Hospital). * At the end of cycle 1, CT scans will be performed to evaluate the participants disease status before they receive combination gemcitabine and bevacizumab. If the scans show the tumor has reduced in size and can be surgically removed, then surgery will be scheduled and the patient will receive gemcitabine and bevacizumab about 4 weeks after the surgery. If the scans show the tumor can not be removed, the patient will receive the gemcitabine/bevacizumab combination about 4 weeks after completing cycle 1. * Cycles 2-5 consist of: gemcitabine given intravenously on days 1, 8, and 15 every 28 days; bevacizumab given intravenously on days 1 and 15 every 28 days. During cycles 2-5 the following tests and procedures will be performed: physical examination including vital signs on day 1 and 15 of each cycle; blood work on days 1, 8 and 15 of each cycle; a urine sample on day 1 of each cycle; CT scans will be done every 2 cycles. * It will take about 7 months to complete the study treatment (longer for those who have surgery after Cycle 1).

Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma

DRUG: bevacizumab
DRUG: 5-Fluorouracil
DRUG: Oxaliplatin
DRUG: gemcitabine
PROCEDURE: External Beam Radiation Therapy

05-233

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2006-03-24	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2009-08-07
First Submitted that Met QC Criteria 2006-03-24	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2009-08-10
First Posted (ESTIMATED) 2006-03-28	Results First Posted N/A	Last Verified 2009-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Factorial

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Regimen Level 1 Radiation/Oxaliplatin/5-FU	DRUG: bevacizumab Intravenously on days 1, 15 and 29 of the first cycle. Intravenously on days 1, 15 of each 28-day cycles for cycles 2-5. DRUG: 5-Fluorouracil Continuous infusion on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-38 of cycle one. DRUG: Oxaliplatin Intravenously on dasy 1, 8, 15, 22, 29, 36 of cycle one. DRUG: gemcitabine Intravenously on days 1, 8, 25 of every 28-day cycle for cycles 2-5. PROCEDURE: External Beam Radiation Therapy Monday through Friday ending on day 38 of cycle 1
EXPERIMENTAL: Regimen Level 2 Radiation/Oxaliplatin/Bevacizumab/5-FU	DRUG: bevacizumab Intravenously on days 1, 15 and 29 of the first cycle. Intravenously on days 1, 15 of each 28-day cycles for cycles 2-5. DRUG: 5-Fluorouracil Continuous infusion on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-38 of cycle one. DRUG: Oxaliplatin Intravenously on dasy 1, 8, 15, 22, 29, 36 of cycle one. DRUG: gemcitabine Intravenously on days 1, 8, 25 of every 28-day cycle for cycles 2-5. PROCEDURE: External Beam Radiation Therapy Monday through Friday ending on day 38 of cycle 1

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Regimen Level 1

Radiation/Oxaliplatin/5-FU

DRUG: bevacizumab

Intravenously on days 1, 15 and 29 of the first cycle. Intravenously on days 1, 15 of each 28-day cycles for cycles 2-5.

DRUG: 5-Fluorouracil

Continuous infusion on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-38 of cycle one.

DRUG: Oxaliplatin

Intravenously on dasy 1, 8, 15, 22, 29, 36 of cycle one.

DRUG: gemcitabine

Intravenously on days 1, 8, 25 of every 28-day cycle for cycles 2-5.

PROCEDURE: External Beam Radiation Therapy

Monday through Friday ending on day 38 of cycle 1

EXPERIMENTAL: Regimen Level 2

Radiation/Oxaliplatin/Bevacizumab/5-FU

DRUG: bevacizumab

Intravenously on days 1, 15 and 29 of the first cycle. Intravenously on days 1, 15 of each 28-day cycles for cycles 2-5.

DRUG: 5-Fluorouracil

Continuous infusion on days 1-5, 8-12, 15-19, 22-26, 29-33 and 36-38 of cycle one.

DRUG: Oxaliplatin

Intravenously on dasy 1, 8, 15, 22, 29, 36 of cycle one.

DRUG: gemcitabine

Intravenously on days 1, 8, 25 of every 28-day cycle for cycles 2-5.

PROCEDURE: External Beam Radiation Therapy

Monday through Friday ending on day 38 of cycle 1

Primary Outcome Measures	Measure Description	Time Frame
To determine the safety and tolerability of the combination of bevacizumab, 5-FU, oxaliplatin, and EBRT for locally advanced pancreatic cancer		2 years
to determine the survival of patients treated with this regimen.

Secondary Outcome Measures	Measure Description	Time Frame
To determine the progression free survival
to determine the rate of conversion to resectability after treatment		2 years
to asses the duration of response and response rate of this combination and
to evaluate the toxicities.		2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically and radiologically confirmed locally advanced pancreatic ductal adenocarcinoma and have not received prior therapy
Disease is measurable by CT scan
Age >= to 18 years
Life expectancy of 4 months or longer
ANC >/= 1,500mm/cm3
Hemoglobin >/= 9g/dl
Platelet count >/= 100,000/cm3
Total bilirubin
SGOT/SGPT
Serum creatinine < 2mg/dl
No evidence of metastatic disease by laparoscopy

History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk for complications
No secondary malignancies other than non-melanoma skin cancers or carcinoma in-situ of the cervix within past 5 years
Patients with pre-existing peripheral neuropathy of grade 2 or greater
Pregnant or lactating women
Current, recent (within 4 weeks of study entry) or planned participation in an experimental drug study
Blood pressure of >150/100 mmHg
Unstable angina
New York Heart Association 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
Presence of central nervous system or brain metastases
Major surgical procedure, open biopsy,m or significant traumatic injury within 28 days prior to day 0
Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
Urine protein creatinine ratio > or = to 1.0 at screening
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0
Serious, non-healing wound, ulcer, or bone fracture

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Genentech, Inc.
Sanofi

Investigators

PRINCIPAL_INVESTIGATOR: Lawrence S. Blaszkowsky, MD, Massachusetts General Hospital

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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