Official Title: “Phase II Trial of Bevacizumab, Gemcitabine, Oxaliplatin in Patients With Metastatic Pancreatic Adenocarcinoma of the Pancreas”

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.

Study Type: Interventional

Study Design: Treatment, Open Label

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.

PROJECTED ACCRUAL: A total of 83 patients will be accrued for this study within 9 months.

Intervention(s) in this Clinical Trial

• Drug: bevacizumab
• Drug: gemcitabine hydrochloride
• Drug: oxaliplatin

Primary Measures

• Survival at 6 months
  • Safety Issue?: No

Secondary Measures

• Objective response rate as measured by RECIST criteria
  • Safety Issue?: No
• Median survival
  • Safety Issue?: No
• Progression-free survival
  • Safety Issue?: No
• Time to treatment failure
  • Safety Issue?: No
• Overall survival
  • Safety Issue?: No
• Toxicity
  • Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: North Central Cancer Treatment Group

Overall Clinical Trial Officials and Contacts

George P. Kim, MD Study Chair Mayo Clinic  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00112528

Study ID Number: CDR0000430845

ClinicalTrials.gov Identifier: NCT00112528

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database