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

Sponsors and Collaborators:	Massachusetts General Hospital Dana-Farber Cancer Institute Beth Israel Deaconess Medical Center Genentech Sanofi-Aventis
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00307723

Purpose

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).

Condition	Intervention	Phase
Pancreatic Cancer Pancreatic Ductal Adenocarcinoma	Drug: bevacizumab Drug: 5-Fluorouracil Drug: Oxaliplatin Drug: gemcitabine Procedure: External Beam Radiation Therapy	Phase I Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Cancer Pancreatic Cancer Radiation Therapy

Drug Information available for: Fluorouracil Oxaliplatin Gemcitabine Gemcitabine hydrochloride Bevacizumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Factorial Assignment, Safety/Efficacy Study
Official Title:	A Tolerability and Efficacy Study of the Angiogenesis Inhibitor Bevacizumab in Combination With 5-Fluorouracil, Oxaliplatin, and External Beam Radiation Therapy Followed by Gemcitabine and Bevacizumab for Locally Advanced Pancreatic Cancer

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

To determine the safety and tolerability of the combination of bevacizumab, 5-FU, oxaliplatin, and EBRT for locally advanced pancreatic cancer [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
to determine the survival of patients treated with this regimen. [ Time Frame: TBD ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the progression free survival [ Time Frame: TBD ] [ Designated as safety issue: No ]
to determine the rate of conversion to resectability after treatment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
to asses the duration of response and response rate of this combination and [ Time Frame: TBD ] [ Designated as safety issue: No ]
to evaluate the toxicities. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	52
Study Start Date:	May 2006
Estimated Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Regimen Level 1: Experimental 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
Regimen Level 2: Experimental 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

Arms

Assigned Interventions

Regimen Level 1: Experimental

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

Regimen Level 2: Experimental

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

Detailed Description:

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).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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 </= 2 times control
SGOT/SGPT </= 2.5 times upper limit of normal
Serum creatinine < 2mg/dl
No evidence of metastatic disease by laparoscopy

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00307723

Contacts

Contact: Lawrence S. Blaszkowsky, MD

617-724-4637

Locations

United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Beth-Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Massachusetts General Hospital

Dana-Farber Cancer Institute

Beth Israel Deaconess Medical Center

Genentech

Sanofi-Aventis

Investigators

Principal Investigator:

Lawrence S. Blaszkowsky, MD

Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	Massachusetts General Hospital ( Lawrence Blaszkowsky< MD )
Study ID Numbers:	05-233
Study First Received:	March 24, 2006
Last Updated:	December 21, 2007
ClinicalTrials.gov Identifier:	NCT00307723 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:

EBRT
advanced pancreatic cancer

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Pancreatic Neoplasms
Bevacizumab
Oxaliplatin
Gemcitabine
Breast Diseases
Endocrine Gland Neoplasms
Digestive System Neoplasms
Skin Diseases
Breast Neoplasms
Endocrine System Diseases
Angiogenesis Inhibitors

Immunosuppressive Agents
Antiviral Agents
Carcinoma
Carcinoma, Ductal
Digestive System Diseases
Radiation-Sensitizing Agents
Fluorouracil
Pancreatic Diseases
Gastrointestinal Neoplasms
Carcinoma, Ductal, Breast
Endocrinopathy
Adenocarcinoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Bevacizumab
Oxaliplatin
Neoplasms by Site
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Gemcitabine

Breast Diseases
Endocrine Gland Neoplasms
Digestive System Neoplasms
Neoplasms by Histologic Type
Skin Diseases
Growth Substances
Endocrine System Diseases
Breast Neoplasms
Enzyme Inhibitors
Angiogenesis Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Carcinoma
Carcinoma, Ductal

ClinicalTrials.gov processed this record on May 07, 2009