Gemcitabine, Cisplatin, And Bevacizumab In Treating Patients With Metastatic Pancreatic Cancer

Study Overview

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

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.

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.

Pancreatic Cancer

BIOLOGICAL: bevacizumab
DRUG: cisplatin
DRUG: gemcitabine hydrochloride

CDR0000437858
UCSF-04451
GENENTECH-AVF2937s

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2005-08-02	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2012-09-13
First Submitted that Met QC Criteria 2005-08-02	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2012-09-17
First Posted (ESTIMATED) 2005-08-04	Results First Posted N/A	Last Verified 2012-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	Time Frame
Time to progression
Duration of response
Overall survival
Toxicity as measured by NCI CTC version 2.0
Micrometastases for predicting time to progression and overall survival

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

18 and over

ECOG 0-2

Not specified

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

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)

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

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

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

Not specified

Not specified

Not specified

Not specified

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Andrew Ko, MD, University of California, San Francisco

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Ko AH, Dito E, Schillinger B, Venook AP, Xu Z, Bergsland EK, Wong D, Scott J, Hwang J, Tempero MA. A phase II study evaluating bevacizumab in combination with fixed-dose rate gemcitabine and low-dose cisplatin for metastatic pancreatic cancer: is an anti-VEGF strategy still applicable? Invest New Drugs. 2008 Oct;26(5):463-71. doi: 10.1007/s10637-008-9127-2. Epub 2008 Apr 1.

Learn

Resources

Patients

Caregivers

Clinical Trial Record