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

Alliance for Clinical Trials in Oncology

Status and phase

Completed

Phase 2

Conditions

Pancreatic Cancer

Treatments

Biological: bevacizumab

Drug: gemcitabine hydrochloride

Drug: oxaliplatin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00112528

NCI-2012-02655 (Registry Identifier)

CDR0000430845 (Registry Identifier)

NCCTG-N034A

Details and patient eligibility

About

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.

Full 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.

Enrollment

53 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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