Imatinib Mesylate in Treating Patients With Gastrointestinal Stromal Tumor That Has Been Completely Removed During Surgery

Gastrointestinal Stromal Tumor Clinical Trial

Official title:

A Phase II Study of Adjuvant STI571 (Gleevec TM) Therapy in Patients Following Completely Resected High-risk Primary GastroIntestinal Stromal Tumor (GIST)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00025246
• Other study ID #: NCI-2012-03079
• Secondary ID: ACOSOG-Z9000U10C
• Status: Completed
• Phase: Phase 2
• First received: October 11, 2001
• Last updated: February 19, 2013
• Start date: September 2001

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase II trial is studying how well imatinib mesylate works in treating patients with gastrointestinal stromal tumor that was completely removed during surgery. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth

Description:

PRIMARY OBJECTIVES:

I. To ascertain whether patients with completely resected high-risk primary GIST who undergo adjuvant treatment with STI571 have prolonged survival compared to historical controls.

SECONDARY OBJECTIVES:

I. To determine the 2 and 5-year prevalence of recurrence in patients treated with adjuvant STI571 following complete resection of high-risk primary GIST.

II. To obtain from patients with GIST: tumor tissue (before therapy with STI571 and at the time of recurrence), blood specimens (before therapy with STI571), and serum specimens (before therapy with STI571, after completing therapy with STI571, and at the time of recurrence) for scientific correlative analyses.

III. To assess the toxicity of oral STI571 therapy when used in the adjuvant setting.

OUTLINE:

Patients receive oral imatinib mesylate daily beginning within 84 days of surgical resection. Treatment continues for 1 year in the absence of disease recurrence or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 10 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Patient must have an ECOG/Zubrod performance status of = 2

• Patient must have a diagnosis of high-risk primary GIST; NOTE: High risk is defined as tumor size = 10 cm in maximum dimension, or the presence of tumor rupture before or during surgery, intraperitoneal hemorrhage or multifocal (< 5) intraperitoneal tumors

• Patient must have undergone complete gross resection (includes R0 [negative microscopic margins] and R1 [positive microscopic margins] resections) of a primary GIST within 70 days prior to registration

• Patient must have a histologic diagnosis of GIST that is confirmed by central pathology review

• Patient's tumor must stain positive for the Kit receptor tyrosine kinase on immunohistochemistry as determined by the central pathologist using the Dako (Dako Corp., Carpinteria, CA) anti-CD 117 antibody

• Patient must have a chest x-ray completed within 28 days prior to registration

• Patient must have a post-operative CT scan with IV and PO contrast or MRI with contrast (if allergic to CT contrast) of abdomen and pelvis within 28 days prior to registration

• Creatinine = 1.5 times the institution ULN

• WBC = 2,000/mm^3

• Platelet = 100,000/mm^3

• Total bilirubin = 1.5 times the institution ULN

• AST and ALT = 2.5 times the institution ULN

• Female of childbearing potential must have negative serum pregnancy test

• Patient or the patient's legally acceptable representative must provide a signed and dated written informed consent prior to registration and any study related procedures

• If patient is a cancer survivor, each of the following criteria must apply:

• Patient has undergone potentially curative therapy for all prior malignancies,

• No evidence of any prior malignancies for at least 5 years with no evidence of recurrence (except for effectively treated basal cell or squamous carcinoma of the skin, carcinoma in-situ of the cervix that has been effectively treated by surgery alone, or lobular carcinoma in-situ of the ipsilateral or contralateral breast treated by surgery alone)

• Patient is deemed by their treating physician to be at low risk for recurrence from prior malignancies

Exclusion Criteria:

• Patient has received post-operative chemotherapy

• Patient has received post-operative radiation therapy

• Patient has received post-operative investigational treatment

• Patient has received prior therapy with STI571

• Patient has had an active infection requiring antibiotics within 14 days prior to registration

• Patient has objective evidence of residual disease on the post-operative CT scan or MRI of the abdomen or pelvis

• Patient, if female and breastfeeding; NOTE: It is not known whether STI571 or its metabolites are excreted in human milk; however, in lactating female rats administered 100 mg/kg, a dose approximately equal to the maximum clinical dose of 800 mg/day based on body surface area, STI571 and/or its metabolites were extensively excreted in milk; it is estimated that approximately 1.5% of a maternal dose is excreted into milk, which is equivalent to a dose to the infant of 30% the maternal dose per unit body weight; because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women should be advised against breastfeeding while taking STI571

• Patient has New York Heart Association class 3 or 4 cardiac disease

• Patient is taking full dose warfarin; NOTE: The use of mini-dose warfarin (1 mg orally per day) for prevention of central line-associated deep venous thrombosis is permitted

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumor
• Gastrointestinal Stromal Tumors

Intervention

Drug:
• imatinib mesylate
Given orally

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	American College of Surgeons Oncology Group	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination whether patients with completely resected high-risk primary GIST who undergo adjuvant treatment with imatinib mesylate have prolonged survival compared to historical controls		Up to 5 years	No
Secondary	Prevalence of recurrence free survival	Marginal point and two-sided 95% (pointwise) confidence bands, based on Kaplan-Meier estimator will be produced.	2 years	No
Secondary	Prevalence of recurrence	Marginal point and two-sided 95% (pointwise) confidence bands, based on Kaplan-Meier estimator will be produced.	5 years	No
Secondary	Overall survival	Marginal point and two-sided 95% (pointwise) confidence bands, based on Kaplan-Meier estimator will be produced.	Up to 5 years	No
Secondary	Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria		Up to 10 years	Yes