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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastrointestinal Stromal Tumor
• Intervention / Treatment: Drug: Sorafenib Tosylate

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Springfield, Illinois, United States, 62702
      • Central Illinois Hematology Oncology Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (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.	Drug: Sorafenib Tosylate; Other Names: BAY 54-9085; Nexavar; BAY 43-9006 Tosylate; sorafenib; BAY 54 9085; BAY 549085; BAY-54-9085; BAY549085

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Hedy L Kindler, University of Chicago Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2005
• Primary Completion (Actual): February 11, 2010
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: December 14, 2005
• First Submitted That Met QC Criteria: December 14, 2005
• First Posted (Estimated): December 15, 2005

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amides; Benzene Derivatives; Urea; Acids, Heterocyclic; Phenylurea Compounds; Niacinamide; Nicotinic Acids; Sorafenib
• Other Study ID Numbers: NCI-2009-00116 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62201 (U.S. NIH Grant/Contract); P30CA014599 (U.S. NIH Grant/Contract); N01CM62207 (U.S. NIH Grant/Contract); N01CM62209 (U.S. NIH Grant/Contract); N01CM62206 (U.S. NIH Grant/Contract); NCI-7028; CDR0000739566; 13780A (Other Identifier: University of Chicago Comprehensive Cancer Center); 7028 (Other Identifier: CTEP)