Bevacizumab, Gemcitabine, and Oxaliplatin in Treating Patients With Metastatic Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with gemcitabine and oxaliplatin may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with gemcitabine and oxaliplatin works in treating patients with metastatic pancreatic cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the 6-month survival of patients with metastatic adenocarcinoma of the pancreas treated with bevacizumab, gemcitabine, and oxaliplatin. Secondary Determine the objective response rate in patients with measurable disease treated with this regimen. Determine median survival, progression-free survival, time to treatment failure, and overall survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive gemcitabine IV over 100 minutes and bevacizumab IV over 30-90 minutes on days 1 and 15. Patients also receive oxaliplatin IV over 120 minutes on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 courses of therapy beyond CR. After completion of study treatment, patients are followed every 3-6 months for up to 5 years.

Official Title
-----------------
Phase II Trial of Bevacizumab, Gemcitabine, Oxaliplatin in Patients With Metastatic Pancreatic Adenocarcinoma

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Biological: bevacizumab
* Drug: gemcitabine hydrochloride
* Drug: oxaliplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed ductal cell or undifferentiated adenocarcinoma of the pancreas Previously untreated metastatic disease No islet cell or acinar cell carcinoma or cystadenocarcinoma No invasion of adjacent organs (i.e., duodenum or stomach) or major blood vessels ( i.e., superior mesenteric artery or celiac artery) No CNS metastasis PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 6 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10.0 g/dL No bleeding diathesis or uncontrolled coagulopathy No bleeding events within the past 6 months Hepatic Bilirubin ≤ 2 times upper limit of normal (ULN) (stenting allowed) AST ≤ 5 times ULN No esophageal varices Renal Creatinine ≤ 2 times ULN Proteinuria < 1+ by dipstick or urinalysis OR Protein < 1 g/24-hr urine collection No nephrotic syndrome Cardiovascular No New York Heart Association class II-IV congestive heart failure No symptomatic, unstable angina, or coronary artery disease No uncontrolled cardiac arrhythmias No myocardial infarction within the past 6 months No uncontrolled hypertension No history of cerebrovascular events No clinically significant peripheral arterial disease No other clinically significant cardiac disease Pulmonary No hemoptysis within the past 6 months Immunologic No history of allergy or hypersensitivity to bevacizumab, oxaliplatin, or gemcitabine No hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies No known allergy to other platinum compounds No ongoing or active infection Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after completion of study treatment No serious, non-healing wound, ulcer, or bone fracture No pre-existing peripheral neuropathy > grade 1 No other malignancy within the past 5 years except basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or prostate cancer with a Gleason score < 7 No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness No gastrointestinal bleeding within the past 6 months No unresolved physical trauma within the past 4 weeks PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 months since prior immunotherapy or biologic therapy No prior adjuvant bevacizumab No concurrent immunotherapy No concurrent colony-stimulating factors during the first course of study therapy Chemotherapy Recovered from prior chemotherapy More than 4 months since prior adjuvant chemotherapy for completely resected disease At least 4 months since prior chemoradiotherapy for locally advanced disease More than 4 months since prior gemcitabine as a radiosensitizer or as maintenance therapy No prior cytotoxic chemotherapy for metastatic disease No prior adjuvant oxaliplatin No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy See Chemotherapy More than 4 months since prior radiotherapy No prior radiotherapy to > 25% of bone marrow No prior radiotherapy to sole site of measurable disease unless there is radiologically confirmed progression of the irradiated tumor No concurrent radiotherapy Surgery More than 4 weeks since prior major surgery or trauma and recovered No concurrent surgery Other More than 2 weeks since prior and no concurrent thrombolytic agents Anticoagulation therapy with warfarin or low molecular weight heparin is allowed provided the following criteria are met: At least 2 weeks at a stable dose INR 2-3 No active bleeding or pathologic condition that confers a high risk of bleeding (e.g., tumor involving major vessels or known varices) No recent or concurrent participation in another study of experimental drugs

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gemcitabine + bevacizumab + oxaliplatin<br>Patients receive gemcitabine IV over 100 minutes and bevacizumab IV over 30-90 minutes on days 1 and 15. Patients also receive oxaliplatin IV over 120 minutes on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 courses of therapy beyond CR. After completion of study treatment, patients are followed every 3-6 months for up to 5 years. | Biological: bevacizumab<br> <br> Drug: gemcitabine hydrochloride<br> <br> Drug: oxaliplatin<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 6 months |  | at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate as measured by RECIST criteria |  | Up to 5 years | 
| Median survival |  | Up to 5 years | 
| Progression-free survival |  | Up to 5 years | 
| Time to treatment failure |  | Up to 5 years | 
| Overall survival |  | Up to 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
duct cell adenocarcinoma of the pancreas, recurrent pancreatic cancer, stage IV pancreatic cancer