Sorafenib in Treating Patients With Malignant Gastrointestinal Stromal Tumor That Progressed During or After Previous Treatment With Imatinib Mesylate and Sunitinib Malate

Study Overview
=================
Brief Summary
-----------------
This phase II trial is studying how well sorafenib works in treating patients with malignant gastrointestinal stromal tumor that progressed during or after previous treatment with imatinib mesylate and sunitinib malate. 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.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To determine the objective response rate of patients with imatinib and sunitinib-resistant malignant gastrointestinal stromal tumor who are treated with BAY 43-9006. SECONDARY OBJECTIVES: I. To determine the toxicity experienced by patients with imatinib and sunitinib -resistant malignant gastrointestinal stromal tumor who are treated with BAY 43-9006. II. To determine progression-free survival and overall survival in patients with imatinib and sunitinib -resistant malignant gastrointestinal stromal tumor who are treated with BAY 43-9006. TERTIARY OBJECTIVES: I. To examine if mutational status of KIT and PDGFA in patients with imatinib- and sunitinib resistant malignant gastrointestinal stromal tumor correlate with response to BAY 43-9006. OUTLINE: This is a multicenter study. Patients are stratified according to response to prior treatment with imatinib mesylate and sunitinib malate (imatinib mesylate- and sunitinib malate-responsive disease vs primary imatinib mesylate- and sunitinib malate-refractory disease). Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.

Official Title
-----------------
A Phase 2 Study of BAY 43-9006 for Imatinib- and Sunitinib Resistant Gastrointestinal Stromal Tumor

Conditions
-----------------
Gastrointestinal Stromal Tumor

Intervention / Treatment
-----------------
* Drug: Sorafenib Tosylate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed gastrointestinal stromal tumor Not amenable to curative surgery Kit-expressing tumor Disease progression (i.e., new lesion or 20% increase in unidimensional tumor size) on or after treatment with imatinib mesylate and sunitinib malate Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques OR > 10 mm by spiral CT scan Only site of measurable disease must be outside of previously irradiated area No known brain metastases Performance status - ECOG 0-2 More than 3 months Absolute neutrophil count > 1,500/mm^3 Platelet count > 100,000/mm^3 Bilirubin normal AST and ALT < 2.5 times upper limit of normal Creatinine ≤ 1.5 mg/dL Creatinine clearance > 60 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled hypertension Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness No evidence of bowel perforation or obstruction No prior angiogenesis inhibitors No immunotherapy after the last dose of imatinib mesylate or sunitinib malate No chemotherapy or chemoembolization therapy after the last dose of imatinib mesylate or sunitinib malate See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered At least 14 days since prior imatinib mesylate or sunitinib malate No prior sorafenib No prior inhibitors of MAPK-signaling intermediates No other investigational agent after the last dose of imatinib mesylate or sunitinib malate Concurrent anticoagulation therapy with warfarin allowed provided the following criteria are met: On a therapeutic stable warfarin dose INR ≤3 No active bleeding or pathologic condition that confers a high risk of bleeding No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent administration of any of the following: Enzyme-inducing antiepileptic drugs (e.g., carbamazepine, phenytoin, or phenobarbital) Hypericum perforatum (St. John's wort) Rifampin No other concurrent anticancer agents or 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)<br>Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: Sorafenib Tosylate<br> <br> * Other names: sorafenib;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response (complete response (CR)+ partial response (PR)) will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR is the disappearance of all target lesions. PR requires at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Computed Tomography (CT) scans for disease reassessment will be obtained pre-therapy and every 8 weeks. In addition to a baseline scan, confirmatory scans will also be obtained 4 weeks following initial documentation of objective response. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival will be defined as time from the start of treatment until progression (documented according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria and defined as at least a 20% increase in the sum of the longest diameter of target lesions) or death, whichever comes first. CT scans for disease reassessment will be obtained pre-therapy and every 8 weeks. | Up to 5 years | 
| Overall Survival | Overall survival will be defined as time from the start of treatment until death from any cause. | Up to 5 years |