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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Gastrointestinal Stromal Tumor	Drug: Sorafenib Tosylate	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	38 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 2 Study of BAY 43-9006 for Imatinib- and Sunitinib Resistant Gastrointestinal Stromal Tumor
Actual Study Start Date :	September 14, 2005
Actual Primary Completion Date :	February 11, 2010

Arms and Interventions

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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 43-9006 Tosylate; BAY 54-9085; Nexavar; sorafenib

Outcome Measures

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Primary Outcome Measures :

1. Objective Response Rate [ Time Frame: 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 :

1. Progression-free Survival [ Time Frame: 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.

2. Overall Survival [ Time Frame: Up to 5 years ]
   Overall survival will be defined as time from the start of treatment until death from any cause.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

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

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Hedy Kindler	University of Chicago Comprehensive Cancer Center

More Information

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Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00265798 History of Changes
Other Study ID Numbers:	NCI-2009-00116; NCI-2009-00116 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); NCI-7028; CDR0000739566; 13780A ( Other Identifier: University of Chicago Comprehensive Cancer Center ); 7028 ( Other Identifier: CTEP ); N01CM62201 ( U.S. NIH Grant/Contract ); N01CM62206 ( U.S. NIH Grant/Contract ); N01CM62207 ( U.S. NIH Grant/Contract ); N01CM62209 ( U.S. NIH Grant/Contract ); P30CA014599 ( U.S. NIH Grant/Contract )
First Posted:	December 15, 2005
Results First Posted:	January 21, 2014
Last Update Posted:	October 2, 2018
Last Verified:	September 2018

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Sorafenib; Sunitinib; Imatinib Mesylate; Niacinamide	Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Vitamin B Complex; Vitamins; Micronutrients; Growth Substances; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Inhibitors