Study of Dose Escalation Versus no Dose Escalation of Imatinib in Metastatic Gastrointestinal Stromal Tumors (GIST) Patients

Official Title: “A Randomized, Phase 3 Study of Dose Escalation Versus No Dose Escalation of Imatinib In Metastatic GIST Patients With Imatinib Trough Levels Less Than 1100 Nanograms/mL”

The purpose of this study is to determine if escalating the dose of imatinib to keep the drug blood level at ≥ 1100 ng/ml leads to better outcomes for patients.

Intervention(s) in this Clinical Trial

• Drug: Imatinib mesylate
  • 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops
• Drug: Imatinib mesylate
  • 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops
• Drug: Imatinib mesylate
  • 400, 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Arm A
  • Patients with blood level less than 1100 will continue imatinib 400 mg daily
• Active Comparator: Arm B
  • Patients with blood level less than 1100 dose adjust imatinib mesylate to goal blood level ≥1100 ng/mL
• Active Comparator: Arm C
  • Patients with blood level ≥1100 will continue imatinib 400 mg daily
• Active Comparator: Arm D
  • Patients with tumors that harbor exon 9 mutations will continue imatinib mesylate at 400 mg or dose escalate up to 800 mg daily

Primary Measures

• Evaluation of lesions for progression or response via RECIST criteria
  • Time Frame: Every 3 months
    Safety Issue?: No

Inclusion Criteria:

• Age ≥ 18 years
• Unresectable and/or metastatic GIST
• Currently receiving imatinib 400 mg per day for a minimum of 4 weeks prior to registration, and for no more than 6 months prior to registration. This must be the first time that the patient has been treated for metastatic and/or unresectable GIST
• For patients who received imatinib following surgery at the time of an initial diagnosis of GIST, there must be a 6 month interval between completion of imatinib and the diagnosis of metastatic GIST
• Good physical functioning (ECOG Performance Status of 0 or 1)
• Generally, good function of organ such as liver and kidneys

Exclusion Criteria:

• Disease progression during adjuvant therapy with imatinib (adjuvant treatment is treatment that is given after surgery for GIST)
• Known intolerance of imatinib at a dose of 400 mg/day or higher
• Prior systemic therapy for advanced GIST with imatinib or those who have been on imatinib for longer than 6 months for unresectable and/or metastatic disease
• Major surgery within 2 weeks prior to Day 1 of study or who have not yet recovered from prior surgery
• Use of coumadin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)
• Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation < 2 weeks or who have not recovered from side effects of this therapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Sarcoma Alliance for Research through Collaboration Other

Overall Clinical Trial Officials and Contacts

Suzanne George, MD Principal Investigator Dana-Farber Cancer Institute  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01031628

Study ID Number: SARC019

ClinicalTrials.gov Identifier: NCT01031628

Health Authority: United States: Institutional Review Board

SARC Website