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

PURPOSE: This randomized phase II is studying how well giving sorafenib with or without gemcitabine works in treating patients with metastatic pancreatic cancer.

Condition	Intervention	Phase
recurrent 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 metastatic pancreatic carcinoma treated with gemcitabine and sorafenib or sorafenib alone followed by gemcitabine and sorafenib at disease progression.

Secondary

• Determine the 6-month overall survival rate, 3-month progression-free survival rate, time to disease progression, and overall survival of patients treated with these regimens.
• Compare the safety profile of gemcitabine and sorafenib with that of single-agent sorafenib in these patients.
• Correlate mRNA expression levels of genes involved in the gemcitabine pathway (RR, dck, and dcd) and genes involved in the Raf pathway (cyclin D, vascular endothelial growth factor receptor-2 [VEGFR-2] and p21) with time to progression, overall survival, and response in patients treated with these regimens.
• Correlate genomic polymorphisms of genes involved in the gemcitabine pathway (RR) and genes involved in the Ras pathway (measured in peripheral blood mononuclear cells) with time to progression, overall survival, tumor response, and adverse events in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to arm II.
• Arm II: Patients receive oral sorafenib as in arm I and gemcitabine IV over 100 minutes on days 1, 8, and 15. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: Approximately 24-74 patients (12-37 per treatment arm) will be accrued for this study within 15 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed pancreatic carcinoma
• Metastatic disease
• Cannot be completely resected by surgery
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Tumor accessible for biopsy OR paraffin embedded tissue available
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

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
• Hemoglobin ≥ 9 mg/dL
• No evidence of bleeding diathesis

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN (5 times ULN in patients with liver involvement of tumor)

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

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

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to, during, and for 6 months after study participation
• No other uncontrolled illness
• No other primary malignancy within the past 5 years except carcinoma in situ of the cervix, prostate, or breast or adequately treated nonmelanoma skin cancer
• No psychiatric illness or social situation that would preclude study compliance
• No ongoing or active infection
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drugs

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for metastatic disease
• More than 6 months since prior adjuvant chemotherapy
• No prior gemcitabine

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No concurrent combination anti-retroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No concurrent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, or ritonavir)
• No concurrent therapeutic anticoagulation
• Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed
• No other concurrent anticancer therapy

Please refer to this study by ClinicalTrials.gov identifier  NCT00114244

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      City of Hope Medical Group, Pasadena,  California,  91105,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States; Recruiting
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting

Study chairs or principal investigators

Heinz-Josef Lenz, MD,  Study Chair,  University of Southern California   

Study ID Numbers:  CDR0000433041; CCC-PHII-50; NCI-6576; NCT00114244
Record last reviewed:  June 2005
Last Updated:  June 30, 2005
Record first received:  June 13, 2005
ClinicalTrials.gov Identifier:  NCT00114244
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-05