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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00265798
First received: December 14, 2005
Last updated: June 2, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Gastrointestinal Stromal Tumor
Drug: sorafenib tosylate
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of BAY 43-9006 for Imatinib- and Sunitinib Resistant Gastrointestinal Stromal Tumor

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

    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:
  • Progression-free Survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

    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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Overall survival will be defined as time from the start of treatment until death from any cause.


Enrollment: 38
Study Start Date: September 2005
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (sorafenib tosylate)
Patients receive oral sorafenib 400mg 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
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN

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 400mg 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 - Eastern Cooperative Oncology Group (ECOG) 0-2
  • More than 3 months
  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Bilirubin <= upper limit of normal
  • aspartate aminotransferase (AST) and alanine aminotransferase (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 mitogen-activated protein kinase (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
    • International Normalized Ratio (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00265798

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
Investigators
Principal Investigator: Hedy Kindler University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00265798     History of Changes
Other Study ID Numbers: NCI-2009-00116, NCI-2009-00116, NCI-7028, CDR0000739566, 13780A, 7028, N01CM62201, N01CM62206, N01CM62207, N01CM62209
Study First Received: December 14, 2005
Results First Received: December 6, 2013
Last Updated: June 2, 2014
Health Authority: United States: Food and Drug Administration

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
Niacinamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 29, 2014