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

Phase 2

Active, not recruiting

Conditions: Gastrointestinal Stromal Tumor

Interventions: Drug: Sorafenib Tosylate

Registration Number: NCT00265798

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 38

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (sorafenib tosylate)	Sorafenib Tosylate	Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	Up to 5 years	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.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	Up to 5 years	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.
Overall Survival	Up to 5 years	Overall survival will be defined as time from the start of treatment until death from any cause.

Trial Locations

Locations (6): Central Illinois Hematology Oncology Center
🇺🇸
Springfield, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States