Preoperative and Postoperative Imatinib Mesylate Study in Patients With c-Kit Positive GIST

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by:
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00500188
First received: July 10, 2007
Last updated: August 4, 2011
Last verified: August 2011
  Purpose

Primary objectives

  1. To determine whether induction of apoptosis or inhibition of angiogenesis are involved in the antitumor activity of (Gleevec, Formerly STI-571) in patients with gastrointestinal stromal tumors (GIST) as assessed by Positron Emission Tomography (PET) scanning.
  2. To determine whether dynamic computed tomography (CT), PET scan, molecular and histopathologic responses in GIST tumors from patients treated with Gleevec predict Disease-Free Survival (DFS) time.

Secondary objectives

  1. To determine the disease free survival of patients with resectable or partially resectable gastrointestinal stromal tumors treated with Gleevec preoperatively and continued for 2 years after resection of disease.
  2. To assess the safety and tolerability of Gleevec given to patients with GI stromal tumors 3, 5, or 7 days preoperatively and continued postoperatively.

Condition Intervention Phase
Gastrointestinal Stromal Tumors
Drug: Imatinib Mesylate (Gleevec)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Phase II Study of Preoperative Plus Postoperative Imatinib Mesylate (Gleevec, Formerly STI-571) in Patients With Primary, Recurrent, or Metastatic Resectable, Kit-Expressing, Gastrointestinal Stromal Tumor (GIST)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Disease-free survival (DFS) time [ Time Frame: Baseline start of therapy to 2 years postoperative Gleevec or disease progression. ] [ Designated as safety issue: No ]
    Effect of drug imatinib mesylate on gastrointestinal stromal tumors (GIST) by disease-free survival (DFS) time, measured from the start of Gleevec therapy, among the three arms to disease progression or 2 years postoperative therapy, measured in months.


Enrollment: 28
Study Start Date: July 2003
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 7 Days
Imatinib Mesylate 300 mg orally twice daily starting 7 days before surgery.
Drug: Imatinib Mesylate (Gleevec)
300 mg orally twice daily
Other Names:
  • Gleevec
  • STI-571
  • Imatinib
  • NSC-716051
Experimental: 5 Days
Imatinib Mesylate 300 mg orally twice daily starting 5 days before surgery.
Drug: Imatinib Mesylate (Gleevec)
300 mg orally twice daily
Other Names:
  • Gleevec
  • STI-571
  • Imatinib
  • NSC-716051
Experimental: 3 Days
Imatinib Mesylate 300 mg orally twice daily starting 3 days before surgery.
Drug: Imatinib Mesylate (Gleevec)
300 mg orally twice daily
Other Names:
  • Gleevec
  • STI-571
  • Imatinib
  • NSC-716051

Detailed Description:

Imatinib mesylate is a drug that may help to kill gastrointestinal stromal tumor cells.

Around 3 weeks before your scheduled surgery, you will have a PET scan, a CT scan and two to three tablespoons of blood will be collected. These are imaging tests and are being done to check on the status of the disease. These tests will be repeated the day before your scheduled surgery. If your doctor feels it is necessary, you will have a chest x-ray and 2 to 3 tablespoons of blood will be collected for routine tests. Women who are able to have children must have a negative blood pregnancy test.

Before treatment, you will also have a biopsy procedure of the tumor performed. This biopsy is being done to study the effect of imatinib mesylate on the tumor cells. The tissue that is collected during the biopsy procedure will be compared to the tumor that is taken out at the time of surgery.

You will be randomly assigned (as in the toss of a coin) to one of three groups. One group will begin taking imatinib mesylate two times a day by mouth starting 7 days before surgery. The second group will start taking imatinib mesylate 5 days before surgery. Participants in the third group will begin taking imatinib mesylate 3 days before surgery. After your surgery, the removed tumor will be studied and compared to the tissue collected before surgery to see what effect (if any) imatinib mesylate had on the tumor. All patients will then continue imatinib mesylate for 2 years after surgery.

You will take imatinib mesylate two times a day for 2 years.

If you develop any side effects to the study drug, treatment may be temporarily stopped or the dose of the drug changed until the symptoms are gone. If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you.

You will be seen by a physician regularly after surgery. Two to three tablespoons of blood will be collected once a month for routine tests, and a you will have a CT scan done every 3 months. These tests will help us determine if your cancer has come back.

THIS IS AN INVESTIGATIONAL STUDY. Imatinib mesylate is FDA approved and is commercially available. Up to 48 participants will take part in this study. All will be enrolled at M. D. Anderson.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent.
  2. Patients must have a histologically proven diagnosis of primary, locally advanced and/or metastatic GIST for which complete or partial resection is planned by a MDACC sarcoma surgeon.
  3. Patients must have immunohistochemical documentation of kit expression in the tumor using the DAKO A4502 or other acceptable antibody.
  4. Patients must have a least one lesion greater than 1 cm that can be accurately measured in one dimension by plain radiograph, CT or magnetic resonance imaging (MRI).
  5. Patients must have normal organ and marrow function (White blood count-WBC greater than or equal to 3,000/ul, Absolute neutrophil count (ANC) greater than or equal to 1500/ul, platelets greater than or equal to 100,00/ul, total bilirubin less than or equal to 1.5 * Upper Limits of Normal (ULN), aspartate aminotransferase (AST or SGOT) or alanine aminotransferase (ALT or SGPT) less than or equal to 2.5 * ULN, serum creatinine less than or equal to 1.5 * ULN).
  6. Patients must have a serum glucose < 200 mg/dl prior to PET scan. Patients must be able to lie flat and still for the PET scan.
  7. Patients may not have any uncontrolled medical or psychiatric conditions that would make the patient unable to tolerate therapy. Patients with uncontrolled medical conditions or psychiatric conditions may have informed consent granted by a legal guardian or surrogate decision maker.
  8. Patients may not have any prior malignancy in the past 5 years other than non-melanoma skin cancer, cervical cancer in situ, or any other malignancy that is not currently clinically significant.
  9. Zubrod performance status of 0 - 3.
  10. May not have metastases outside of the peritoneal cavity.
  11. If patients have any signs or symptoms of metastases, the appropriate workup should occur prior to enrollment (eg, CT of the head for a patient with central nervous system (CNS) symptoms).
  12. Patients may not have had chemotherapy, radiotherapy, biological therapy or any investigational drugs 3 weeks prior to the study.
  13. Women should have a negative pregnancy test within 7 days of study opening.
  14. Patients must agree to use an effective contraceptive method.

Exclusion Criteria:

  1. Prior treatment using Gleevec.
  2. Patients with Class III or Class IV New York Heart Association congestive heart failure.
  3. Pregnant or nursing women.
  4. Patients taking therapeutic doses of Coumadin for anticoagulation. Coumadin may be taken but dose should be less than or equal to 1 mg po per day. Patients MAY take a low molecular weight heparin.
  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: NCT00500188

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Investigators
Principal Investigator: Jonathan Trent, MD, PhD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Jonathan Trent, MD, PhD/Assistant Professor, U.T.M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00500188     History of Changes
Other Study ID Numbers: ID03-0023
Study First Received: July 10, 2007
Last Updated: August 4, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Gastrointestinal Stromal Tumors
GIST
Kit expression
Resectable
Imatinib Mesylate
Gleevec
STI-571
Imatinib
NSC-716051

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 28, 2014