Clinical trial NCT00265798: Sorafenib in Treating Patients With Malignant Gastrointestinal Stromal Tumor That Progressed During or After Previous Treatment With Imatinib Mesylate and Sunitinib Malate
Official title: A Phase 2 Study of BAY 43-9006 for Imatinib- and Sunitinib Resistant Gastrointestinal Stromal Tumor
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-12-15
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate
timeFrame: Up to 5 years
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Up to 5 years
measure: Overall Survival
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Hedy L Kindler
role: PRINCIPAL_INVESTIGATOR
References: