Sorafenib and Gemcitabine in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
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. This phase II trial is studying how well giving sorafenib together with gemcitabine works in treating patients with locally advanced or metastatic pancreatic cancer.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. Determine the objective response rate in patients with locally advanced or metastatic adenocarcinoma of the pancreas treated with sorafenib and gemcitabine. II. Determine the toxicity experienced by patients with advanced pancreatic cancer who are treated with sorafenib plus gemcitabine. 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.

Official Title
-----------------
A Phase II Study of BAY 43-9006/Gemcitabine for Advanced Pancreatic Cancer

Conditions
-----------------
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: sorafenib tosylate
* Drug: gemcitabine hydrochloride


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Performance status - ECOG 0-1 Performance status - Karnofsky 70-100% More than 3 months WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No evidence of bleeding diathesis Bilirubin normal AST and/or ALT ≤ 2.5 times upper limit of normal Creatinine normal Creatinine clearance ≥ 60 mL/min No uncontrolled hypertension No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia 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 No prior antiangiogenic agents 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 See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (sorafenib tosylate and gemcitabine hydrochloride)<br>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. | Drug: sorafenib tosylate<br>* Given orally<br>* Other names: SFN;Drug: gemcitabine hydrochloride<br>* Given IV<br>* Other names: Gemzar;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate as measured by RECIST criteria |  | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Kaplan-Meier curves will be constructed. | From start of treatment to progression or death, assessed up to 6 months | 
| Survival | Specific attention will be given to the six-month survival rate, for which 90% confidence intervals will be generated. | At 6 months | 
| Overall survival | Kaplan-Meier curves will be constructed | Up to 6 months |