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

University of California San Francisco (UCSF)

Status and phase

Completed

Phase 2

Conditions

Pancreatic Cancer

Treatments

Drug: cisplatin

Drug: gemcitabine hydrochloride

Biological: bevacizumab

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00126633

CDR0000437858

UCSF-04451

GENENTECH-AVF2937s

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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 tumor cells by blocking blood flow to the tumor. Giving gemcitabine and cisplatin together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gemcitabine and cisplatin together with bevacizumab works in treating patients with metastatic pancreatic cancer.

Full description

OBJECTIVES:

Primary

Determine time to disease progression in patients with previously untreated metastatic adenocarcinoma of the pancreas treated with gemcitabine, cisplatin, and bevacizumab.
Determine the safety and toxicity of this regimen in these patients.

Secondary

Determine the objective response rate in patients treated with this regimen.
Determine the efficacy of this regimen, in terms of the proportion of patients with ≥ a 50% decline in the CA19-9 biomarker, in these patients.
Determine the median survival of patients treated with this regimen.
Correlate serum markers of angiogenesis and circulating tumor micrometastases with clinical outcome of patients treated with this regimen.

OUTLINE: This is an open-label, non-randomized study.

Patients receive gemcitabine IV over 100 minutes, cisplatin IV over 30-60 minutes, and bevacizumab* IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients may receive additional study treatment at the discretion of the investigator.

NOTE: *Patients may continue to receive other components of therapy if bevacizumab is discontinued due to toxicity.

After completion of study treatment, patients are followed at 28 days and then monthly thereafter.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study within 12-18 months.

Enrollment

53 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed adenocarcinoma of the pancreas
- Must have documented extrapancreatic metastases
  - Radiographically measurable disease is not required
Previously untreated disease
No CNS or brain metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa [Epogen®] support allowed)
No evidence of bleeding diathesis or coagulopathy

Hepatic

INR ≤ 1.5 (except for patients receiving full-dose warfarin)
Bilirubin ≤ 2.0 mg/dL
AST or ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)

Renal

Creatinine ≤ 2.0 mg/dL
Urine protein:creatinine ratio ≤ 1

Cardiovascular

No New York Heart Association class II-IV congestive heart failure
No myocardial infarction or stroke within the past 6 months
No uncontrolled hypertension (i.e., blood pressure > 160/110 mm Hg despite antihypertensive therapy)
No unstable angina
No unstable symptomatic arrhythmia requiring medication
- Patients with chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) are eligible
No peripheral vascular disease ≥ grade 2

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 significant traumatic injury within the past 28 days
No serious non-healing wound, ulcer, or bone fracture
No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
No other serious systemic disease
No history of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

More than 28 days since prior major surgery, or open biopsy
More than 7 days since prior fine needle aspirations or core biopsies
No concurrent major surgery

Other

No prior therapy, including systemic or investigational therapy, for locally advanced or metastatic pancreatic cancer
- Treatment given in the adjuvant setting (e.g., radiotherapy and/or chemotherapy, given either concurrently or systemically) is not considered prior therapy provided progressive disease occurred > 6 months after completion of prior treatment
Concurrent continuation of therapeutic doses of warfarin or low-molecular weight heparin allowed for pulmonary embolism, deep vein thrombosis, atrial fibrillation, or other clinical indications provided patients has been on a stable dose for ≥ 28 days with no further clotting or bleeding complications