Imatinib Mesylate With or Without Surgery in Treating Patients With Metastatic Gastrointestinal Stromal Tumor That is Responding to Imatinib Mesylate

This study has been terminated.
(low accrual)
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00956072
First received: August 8, 2009
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

RATIONALE: Surgery may remove residual disease in patients with gastrointestinal stromal tumor that is responding to imatinib mesylate. It is not yet known whether surgery is more effective than continued imatinib mesylate in treating patients with metastatic gastrointestinal stromal tumor.

PURPOSE: This randomized phase III trial is studying giving imatinib mesylate therapy together with surgery to see how well it works compared with imatinib mesylate alone in treating patients with metastatic gastrointestinal stromal tumor that is responding to imatinib mesylate.


Condition Intervention Phase
Gastrointestinal Stromal Tumor
Drug: imatinib mesylate
Procedure: therapeutic conventional surgery
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Phase III Randomized Study Evaluating Surgery of Residual Disease in Patients With Metastatic Gastro-intestinal Stromal Tumor Responding to Imatinib Mesylate.

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Pathological response to imatinib mesylate according to RECIST criteria [ Designated as safety issue: No ]
  • Rate of complete resection [ Designated as safety issue: No ]
  • Surgical morbidity [ Designated as safety issue: Yes ]
  • Quality of life as measured by EORTC QLQ-C30 [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: May 2009
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients undergo surgery of residual disease.
Procedure: therapeutic conventional surgery
Patients undergo surgery
Active Comparator: Arm II
Patients receive imatinib mesylate therapy according to standard of care.
Drug: imatinib mesylate
Patients receive imatinib mesylate

Detailed Description:

OBJECTIVES:

Primary

  • Evaluate whether surgery of residual disease improves the progression-free survival of patients with metastatic gastrointestinal stromal tumor responding to imatinib mesylate.

Secondary

  • Correlate the pharmacokinetics of imatinib mesylate and its metabolites before and after randomization.

OUTLINE: This is a multicenter study. Patients are stratified according to center, site of tumor origin (stomach vs small bowel vs others), and site of metastases (liver vs abdominal cavity vs both). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo surgery of residual disease. Patients will then resume imatinib mesylate therapy according to standard of care as soon as possible after surgery (as soon as the patient restarts taking oral feeding).
  • Arm II: Patients receive imatinib mesylate therapy according to standard of care.

Patients complete quality of life questionnaires at baseline; immediately after hospital discharge (arm I only); and at 5, 11, and 23 months. Blood samples may be collected for pharmacokinetic studies.

After completion of study therapy, patients are followed up every 3 months for 5 years and then every 6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed gastrointestinal stromal tumor expressing CD117+ or with documented mutation of the KIT or PDGFRA gene
  • Metastatic disease (liver and/or abdominal cavity)

    • No extra-abdominal metastases
  • Measurable disease according to RECIST criteria
  • Achieved complete response, partial response, or stable disease without progression since the start of imatinib mesylate therapy, documented according to RECIST
  • Underwent 6-12 months of treatment with imatinib mesylate as a standard of care or within other clinical studies (surgery should be feasible before the end of the 12th month from imatinib mesylate onset)
  • Surgically resectable residual disease as assessed by CT scan and/or MRI within the past 14 days

PATIENT CHARACTERISTICS:

  • WHO performance status 0-1
  • ANC > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Creatinine < 120 μmol/L
  • Albumin > 25 g/L
  • Total bilirubin < 2 times upper limit of normal (ULN)
  • AST and ALT < 2.5 times ULN (< 5 ULN in case of liver metastases)
  • Alkaline phosphatase < 2.5 times ULN (< 5 ULN in case of bone or liver metastases)
  • Negative pregnancy test within the past 14 days
  • Fertile patients must use effective contraception
  • No uncontrolled hypertension (diastolic BP > 95 mm Hg and systolic BP > 170 mm Hg)
  • No myocardial infarction, unstable, or uncontrolled cardiac disease within the past 6 months
  • No history of arterial thrombosis or deep vein thrombosis within the past year
  • No bleeding diathesis, coagulopathy, or major bleeding within the past 6 months
  • No severe and/or uncontrolled concurrent medical disease, including any of the following conditions:

    • Diabetes
    • Chronic renal disease
    • Liver disease, including chronic viral hepatitis judged at risk of reactivation
    • Active infection, including HIV infection
  • No prior malignancy (other than in situ cervical cancer, in situ melanoma, or basal cell or squamous cell cancer of the skin) unless treated with curative intent and without evidence of disease for at least 3 years
  • No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior adjuvant or neo-adjuvant imatinib mesylate or other tyrosine kinase inhibitor
  • No coumadin-type anticoagulant > 2mg/day within the past 7 days
  • No major surgery within the past 28 days
  • No medication that interacts moderately or strongly with the CYP3A system within the past 14 days
  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: NCT00956072

Locations
Italy
European Organization for Research and Treatment of Cancer
Naples, Italy, 80131
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Principal Investigator: Alessandro Gronchi Istituto Nazionale per lo Studio e la Cura dei Tumori
  More Information

No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00956072     History of Changes
Other Study ID Numbers: EORTC-62063, EORTC-62063, EU-20955, EUDRACT-2007-002257-23, NOVARTIS-EORTC-62063
Study First Received: August 8, 2009
Last Updated: September 20, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
gastrointestinal stromal tumor

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
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014