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

October 22, 2020 updated by: National Cancer Institute (NCI)

A Phase II Trial of Neoadjuvant/Adjuvant STI-571 (Gleevec NSC #716051) for Primary and Recurrent Operable Malignant GIST Expressing the KIT Receptor Tyrosine Kinase (CD117)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19103
        • Radiation Therapy Oncology Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
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.
Drug: Imatinib Mesylate
Given orally
Other Names:
  • Gleevec
  • CGP 57148
  • CGP57148B
  • Glivec
  • STI 571
  • STI-571
  • STI571
Procedure: Conventional Surgery
Undergo surgical resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Disease Progression at 2 Years
Time Frame: From 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
From registration to two years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rates of Objective Response (Complete, Partial, and Stable)
Time Frame: 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.
Pretreatment and prior to surgery (at 4-10 weeks, based on surgery timing)
Percentage of Patients With Major Toxicity (Toxicity Grade ≥ 3)
Time Frame: 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.
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.
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 Therapy
Time Frame: change 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.
change from baseline to 1 week post therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Collaborators

Eastern Cooperative Oncology Group
Radiation Therapy Oncology Group
American College of Radiology Imaging Network

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 31, 2002

Primary Completion (Actual)

January 28, 2009

Study Completion (Actual)

January 28, 2009

Study Registration Dates

First Submitted

December 7, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

October 26, 2020

Last Update Submitted That Met QC Criteria

October 22, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02437 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA021661 (U.S. NIH Grant/Contract)
  • ECOG-RTOG-R0132
  • RTOG S-0132
  • ACRIN-6665 (Other Identifier: CIP)
  • CDR0000069111 (CIP)
  • RTOG-S-0132
  • RTOG-0132 (Other Identifier: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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