RATIONALE: Sorafenib may stop the growth of tumor cells by stopping blood flow to the tumor and by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving sorafenib with gemcitabine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving sorafenib together with gemcitabine works in treating patients with locally advanced or metastatic pancreatic cancer.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the pancreas recurrent pancreatic cancer stage II pancreatic cancer stage III pancreatic cancer stage IVA pancreatic cancer stage IVB pancreatic cancer	Drug: gemcitabine  Drug: sorafenib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the objective response rate in patients with locally advanced or metastatic adenocarcinoma of the pancreas treated with sorafenib and gemcitabine.
• Determine the toxicity of this regimen in these patients.

Secondary

• Correlate pre-treatment levels of plasma vascular endothelial growth factor (VEGF), serum basic fibroblast growth factor (bFGF), urine VEGF, and urine bFGF with response, overall survival, and progression-free survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28 and gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 12-35 patients will be accrued for this study within 7 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• Locally advanced or metastatic disease
• Locally advanced disease must extend outside the boundaries of a standard radiotherapy port
• Not amenable to curative surgery or radiotherapy
• Measurable disease
• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Pleural effusion and ascites are not considered measurable lesions
• Outside prior radiotherapy port
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1 OR
• Karnofsky 70-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No evidence of bleeding diathesis

Hepatic

• Bilirubin normal
• AST and/or ALT ≤ 2.5 times upper limit of normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No uncontrolled hypertension
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active or ongoing infection
• No other active malignancy
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib or other study agents
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior antiangiogenic agents

Chemotherapy

• No prior cytotoxic chemotherapy for metastatic disease
• At least 4 weeks since prior adjuvant chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior gemcitabine

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• No prior investigational drugs
• No prior sorafenib
• No prior MAPK signaling agents
• Concurrent warfarin anticoagulation allowed provided the following criteria are met:
• Therapeutic on a stable warfarin dose
• INR ≤ 3
• Undergo weekly INR testing
• No active bleeding or pathological condition that carries a high risk of bleeding
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapies

Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States; Recruiting
      Central Illinois Hematology Oncology Center, Springfield,  Illinois,  62701,  United States; Recruiting
      Decatur Memorial Hospital Cancer Care Institute, Decatur,  Illinois,  62526,  United States; Recruiting
      Evanston Northwestern Health Care - Evanston Hospital, Evanston,  Illinois,  60201-1781,  United States; Recruiting
      Ingalls Cancer Care Center at Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States; Recruiting
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61615-7828,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Michigan
      Oncology Care Associates, P.L.L.C., Saint Joseph,  Michigan,  49085,  United States; Recruiting
New York
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States; Recruiting
North Carolina
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting

Study chairs or principal investigators

Hedy L. Kindler, MD,  Principal Investigator,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000391850; UCCRC-13169B; NCI-6567; NCT00095966
Record last reviewed:  December 2004
Last Updated:  April 4, 2005
Record first received:  November 9, 2004
ClinicalTrials.gov Identifier:  NCT00095966
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08