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Neoadjuvant and Adjuvant Imatinib Mesylate in Treating Patients With Primary or Recurrent Malignant Gastrointestinal Stromal Tumor

Phase 2
Completed
Conditions
Gastrointestinal Stromal Tumor
Interventions
Procedure: Conventional Surgery
Drug: Imatinib Mesylate
Registration Number
NCT00028002
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

Phase II trial to study the effectiveness of neoadjuvant and adjuvant imatinib mesylate in treating patients who are undergoing surgery for primary or recurrent malignant gastrointestinal stromal tumor. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving imatinib mesylate before and after surgery may shrink the tumor so it can be removed and may kill any tumor cells remaining after surgery.

Detailed Description

OBJECTIVES:

I. Determine the progression-free survival of patients with primary or recurrent potentially resectable malignant gastrointestinal stromal tumor treated with neoadjuvant and adjuvant imatinib mesylate.

II. Determine the objective response rate of patients treated with this drug. III. Determine the safety of this drug in these patients.

OUTLINE:

Patients receive oral imatinib mesylate once daily. Treatment continues for 8 weeks in the absence of disease progression. Patients with disease progression are considered for immediate surgical resection. Otherwise, after 8 weeks, patients undergo surgical resection to debulk all gross tumor. Two to four weeks after surgery, patients receive oral imatinib mesylate once daily for 2 years.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
63
Inclusion Criteria

  • Histologically confirmed malignant gastrointestinal stromal tumor

    • Potentially resectable primary disease

    • Potentially resectable recurrent disease

      • Local or intra-abdominal/pelvic metastatic disease

  • Documented c-kit (CD117) expression by immunohistochemical analysis of either initial core specimen or, if recurrent disease, from original tumor block

  • Primary disease must be visceral, intra-abdominal, or pelvic in origin

  • At least 1 unidimensionally measurable lesion

    • At least 5 cm for primary disease
    • At least 2 cm for recurrent disease

  • At least 1 viable core biopsy tumor specimen obtained within 8 weeks before registration

  • Performance status - Zubrod 0-2

  • WBC at least 3,000/mm^3

  • Absolute neutrophil count at least 1,500/mm^3

  • Platelet count at least 100,000/mm^3

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)

  • ALT/AST no greater than 2.5 times ULN

  • No uncontrolled chronic liver disease

  • Creatinine no greater than 1.5 times ULN

  • No uncontrolled chronic renal disease

  • No New York Heart Association class III or IV cardiac disease

  • Must be able to lie still in the PET scanner for approximately 1-2 hours

  • No uncontrollable hyperglycemia

  • No medical or psychological condition that would preclude study participation

  • No severe or uncontrolled medical disease

  • No active uncontrolled infection

  • No known or suspected hypersensitivity to any component of the study drug

  • Any prior malignancy is allowed provided patient remains disease free from that malignancy

  • Not pregnant or nursing

  • Negative pregnancy test

  • Fertile patients must use effective barrier contraception during and for 3 months after study participation

  • At least 28 days since prior biologic therapy

  • No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

  • At least 28 days since prior chemotherapy

  • At least 28 days since prior radiotherapy

  • See Disease Characteristics

  • At least 28 days since prior investigational drugs

  • At least 28 days since prior imatinib mesylate

  • No concurrent therapeutic doses of warfarin

  • Concurrent low-molecular weight heparin or mini-dose warfarin (1 mg per day) prophylaxis is allowed

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm IConventional SurgeryPatients receive oral imatinib mesylate once daily. Treatment continues for 8 weeks in the absence of disease progression. Patients with disease progression are considered for immediate surgical resection. Otherwise, after 8 weeks, patients undergo surgical resection to debulk all gross tumor. Two to four weeks after surgery, patients receive oral imatinib mesylate once daily for 2 years.
Arm IImatinib MesylatePatients receive oral imatinib mesylate once daily. Treatment continues for 8 weeks in the absence of disease progression. Patients with disease progression are considered for immediate surgical resection. Otherwise, after 8 weeks, patients undergo surgical resection to debulk all gross tumor. Two to four weeks after surgery, patients receive oral imatinib mesylate once daily for 2 years.
Primary Outcome Measures
NameTimeMethod
Rate of Disease Progression at 2 YearsFrom registration to two years

Kaplan-Meier estimate of disease progression rate. Disease progression is determined by Response Evaluation Criteria in Solid Tumours criteria (RECIST). RECIST criteria is described here: http://ctep.cancer.gov/protocolDevelopment/docs/recist_guideline.pdf

Secondary Outcome Measures
NameTimeMethod
Percentage of Patients With Major Toxicity (Toxicity Grade ≥ 3)Analysis occurs after all patients have been on study for at least 2 years. Measured from start of treatment to end of follow-up, to a maximum of 4.95 years.

Highest grade toxicity per subject was counted. Toxicities were graded using Common Toxicity Criteria (CTC) v 2.0. Grade refers to the severity of the toxicity, using Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity.

FDG-PET as Biological Marker of Metabolic Response(MR) During Imatinib Mesylate (IM) Treatment, in Patients With GIST Who Are naı¨ve to Tyrosine Kinase Inhibitor Therapychange from baseline to 1 week post therapy

evaluate FDG-PET as a non-invasive functional imaging tool to assess in situ tumor metabolism (as measured by the Standardized Uptake Values of FDG in the tumor) prior to and during the administration of IM. %change in SUVmax \<1 indicate decreased tumor metabolism while values \>1 indicated an increase in tumor metabolism.

Metabolic response by 18F-FDG PET was determined in accordance with the criteria of the European Organization for Research and Treatment of Cancer EORTC), with increases or decreases of more than 25% in SUVmax defining progressive metabolic disease (PMD) and partial metabolic response (PMR), respectively, and new lesions defining PMD.

Rates of Objective Response (Complete, Partial, and Stable)Pretreatment and prior to surgery (at 4-10 weeks, based on surgery timing)

The percentage of patients who achieved a complete, partial or stable response prior to surgery as assessed by Response Evaluation Criteria in Solid Tumours criteria (RECIST). RECIST criteria is described here: http://ctep.cancer.gov/protocolDevelopment/docs/recist_guideline.pdf.

Trial Locations

Locations (1)

Radiation Therapy Oncology Group

🇺🇸

Philadelphia, Pennsylvania, United States

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