Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Imatinib Mesylate (Gleevec; STI571) in Treating Patients With Primary Gastrointestinal Stromal Tumor That Has Been Completely Removed by Surgery

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	ACOSOG-Z9001 CAN-NCIC-SRC1, CALGB-ACOSOG-Z9001, SWOG-ACOSOG-Z9001, NCT00041197, UWCC-UW-6303, UWCC-UW-03-8438-A-03, SRC1

Special Category: CTSU trial

Objectives

Primary

1. Compare the recurrence-free survival of patients with resected primary gastrointestinal stromal tumor treated with adjuvant imatinib mesylate (Gleevec; STI571) vs placebo.

Secondary

1. Compare the overall survival of patients treated with these regimens.
2. Determine the safety and efficacy of adjuvant imatinib mesylate in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed primary gastrointestinal tumor (GIST)



• Tumor size at least 3 cm in maximum dimension



• No peritoneal or distant metastasis



• Prior complete gross resection of a primary GIST within the past 14-70 days
  • R0 resection (negative microscopic margins)

    OR

  • R1 resection (positive microscopic margins)



• Tumor must stain positive for Kit receptor tyrosine kinase by immunohistochemistry using the Dako anti-CD117 antibody



• No objective evidence of residual disease on the postoperative CT scan or MRI of the abdomen or pelvis

Prior/Concurrent Therapy:

Biologic therapy:

• No concurrent anticancer biologic agents

Chemotherapy:

• No prior postoperative chemotherapy
• No concurrent anticancer chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior postoperative radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No prior postoperative investigational treatment
• No prior imatinib mesylate (Gleevec; STI571)
• No other concurrent anticancer agents
• No other concurrent investigational drugs
• No concurrent full-dose warfarin for therapeutic anticoagulation (concurrent mini-dose warfarin [1 mg orally per day] for prophylaxis of central venous catheter thrombosis allowed)

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

  OR

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 2,000/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN) (unless elevation is secondary to Gilbert's disease)
• AST and ALT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

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

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after study participation
• No other malignancy within the past 5 years except:
  • Effectively treated basal cell or squamous cell skin cancer
  • Carcinoma in situ of the cervix effectively treated by surgery alone
  • Lobular carcinoma in situ of the ipsilateral or contralateral breast treated by surgery alone
• Prior malignancies must be deemed at low risk for recurrence
• No active infection requiring antibiotics within the past 14 days

Expected Enrollment

A total of 732 patients will be accrued for this study.

Outcomes

Recurrence-free survival as measured by serial CT scans at 3-6 months

Overall survival as measured by serial doctor visits at 3-6 months

Outline

This is a randomized, double-blind, placebo-controlled, crossover, multicenter study. Patients are stratified according to tumor size (3 cm but less than 6 cm vs 6 cm to less than 10 cm vs 10 cm or greater). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral imatinib mesylate (Gleevec; STI571) once daily. Treatment continues for 1 year in the absence of unacceptable toxicity. Patients who develop a recurrence during the year of initial treatment receive imatinib mesylate (Gleevec; STI571) at an increased dose. Patients who develop a recurrence after the year of initial treatment restart imatinib mesylate (Gleevec; STI571) and continue taking the drug at the discretion of the principal investigator.



• Arm II: Patients receive oral placebo once daily. Treatment continues for 1 year in the absence of unacceptable toxicity. Patients who develop a recurrence at any time discontinue placebo and crossover to arm I. Treatment on arm I continues at the discretion of the principal investigator.

Patients are followed every 3 months for 2 years and then every 6 months for 8 years.

Dematteo RP, Ballman KV, Antonescu CR, et al.: Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 373 (9669): 1097-104, 2009.[PUBMED Abstract]

DeMatteo R, Owzar K, Maki R, et al.: Adjuvant imatinib mesylate increases recurrence free survival (RFS) in patients with completely resected localized primary gastrointestinal stromal tumor (GIST): North American Intergroup phase III trial ACOSOG Z9001. [Abstract] J Clin Oncol 25 (Suppl 18):A-10079, 2007.

ACOSOG Z9001: a phase III randomized double-blind study of adjuvant imatinib mesylate versus placebo in patients following the resection of primary gastrointestinal stromal tumor. Clin Adv Hematol Oncol 2 (5): 310.

Hillman SL, Sargent DJ, Bot, BM, et al.: Questionable value of attribution when interpreting adverse event data: a joint evaluation by North Central Cancer Treatment Group (NCCTG) and American College of Surgeons Oncology Group (ACOSOG). [Abstract] J Clin Oncol 25 (Suppl 18): A-6511, 324s, 2007.

Trial Contact Information

Trial Lead Organizations

American College of Surgeons Oncology Group

Ronald DeMatteo, MD, Protocol chair		Ph: 212-639-5726; 800-525-2225 Email: dematter@mskcc.org

NCIC-Clinical Trials Group

Martin Blackstein, MD, Protocol chair		Ph: 416-586-5371 Email: martin.blackstein@utoronto.ca

Cancer and Leukemia Group B

Christopher Ryan, MD, Protocol chair(Contact information may not be current)		Ph: 773-702-9200; 888-824-0200

Southwest Oncology Group

John Vetto, MD, FACS, Protocol chair		Ph: 503-494-5501; 800-494-1234 Email: vettoj@ohsu.edu

Registry Information
Official Title		A Phase III Randomized Double-Blind Study of Adjuvant STI571 (Gleevec) Versus Placebo in Patients Following the Resection of Primary GastroIntestinal Stromal Tumor (GIST)
Trial Start Date		2002-06-01
Trial Completion Date		2018-04-18 (estimated)
Registered in ClinicalTrials.gov		NCT00041197
Date Submitted to PDQ		2002-05-16
Information Last Verified		2008-08-25
NCI Grant/Contract Number		CA76001

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