Five Year Adjuvant Imatinib Mesylate (Gleevec®) in Gastrointestinal Stromal Tumor (GIST)

A Phase II, Non-Randomized, Open-Label Multicenter Study of 5 Year Adjuvant Imatinib Mesylate (Gleevec®) in Patients at Significant Risk for Recurrence Following Complete Resection of Primary Gastrointestinal Stromal Tumor (GIST)

This is a Phase II, non-randomized, open-label, multi-center study conducted in the USA. The purpose of this trial is to evaluate the use of long term adjuvant imatinib mesylate in patients at significant risk for recurrence following complete resection of primary GIST.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumor (GIST)
• Intervention / Treatment: Drug: imatinib mesylate

Detailed Description

This is a Phase II, non-randomized, open-label, multi-center study conducted in the USA. The primary endpoint is to evaluate the use of long term adjuvant imatinib mesylate in patients at significant risk for recurrence following complete resection of primary GIST. A total of 85 adult patients, 18 years of age and older will be enrolled.Participants will take 400 mg of imatinib mesylate daily by mouth for a total of 5 years. At the conclusion of the treatment period, patients will be followed for 2 years for survival, status of response and antineoplastic treatments and quality of life.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego - Moores Cancer Center Moores UCSD Cancer Center (31)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado University of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center Department of Medical Oncology
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
    • Gainesville, Georgia, United States, 30501
      • Longstreet Cancer Center
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Medical Center Kootenai Cancer Cancer
  • Illinois
    • Evanston, Illinois, United States, 60201
      • North Shore University Health System
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute Dana-Farber
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute Karmonos Cancer Instit. (40)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine Center for Advanced Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Southern Nevada Cancer Research Foundation S. Nevada Cancer Res (2)
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering (7)
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Duke University Med Ctr (8)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University OHS University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State University / Milton S. Hershey Medical Center Penn Stat University
  • Rhode Island
    • Providence, Rhode Island, United States, 02908
      • Roger Williams Medical Center Medical Center
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Kingport Hematology Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (4)
    • San Antonio, Texas, United States, 78259
      • South Texas Oncology and Hematology, PA South Texas Onc/Hem
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates Viriginia Oncology Assoc.

Participation Criteria

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:

1. Patients 18 years of age or older.
2. Patient must have had a histological diagnosis of primary GIST.
3. The tumor must expressed KIT (CD117) protein by immunohistochemistry performed by central pathology.

4. Patient must have been at significant risk of tumor recurrence as defined by either:

   • Primary GIST (any site): ≥ 2 cm and a mitotic rate of ≥ 5/50 HPF's
   • Non-gastric primary GIST: ≥ 5cm
5. Patient must have undergone complete gross resection of a primary GIST within 12 weeks prior to first dose of imatinib study drug. The inclusion of R1 resections will be reviewed on a case by case basis by the Study Management Committee.
6. Patient must had no evidence of metastatic GIST on either 1) a post-operative CT of the abdomen and pelvis with intravenous and oral contrast or 2) MRI of the abdomen and pelvis with intravenous contrast. CT or MRI must have been performed within 8 weeks prior to first dose of imatinib study drug.
7. Performance status 0 or 1 (ECOG)

8. Patient must had the following post-operative laboratory values confirmed within 14 days prior to first dose of imatinib study drug:

   • total bilirubin < 1.5 x ULN NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study.
   • ALT and AST < 2.5 x ULN
   • creatinine < 1.5 x ULN
   • ANC > 1.5 x 109/L
   • platelets > 100 x 109/L

9. If patient is a cancer survivor, ALL of the following criteria apply:

   • Patient had undergone potentially curative therapy for all prior malignancies.
   • No evidence of any prior malignancies for at least 3 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.
10. Female patients of childbearing potential must have had negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients of reproductive potential must have jagreed to employ an effective barrier method of birth control throughout the study and for up to 7 days following discontinuation of study drug.
11. Written, voluntary informed consent.

Exclusion Criteria:

1. Patient has metastatic GIST to the peritoneum, liver, lymph node, or other sites or recurrent GIST.
2. Prior treatment for GIST with the exception of prior treatment with imatinib adjuvant lasting ≤ 8 weeks following gross surgical resection.
3. Patient has received any other investigational agents within 28 days of first day of study drug dosing.
4. Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
5. Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risk or compromise compliance with the protocol (i.e., uncontrolled diabetes, chronic renal disease, chronic liver disease, or active uncontrolled infection).
6. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
7. Patient receiving concurrent treatment with warfarin (acceptable alternative: low-molecular weight heparin).

8. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

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Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imatinib; All subjects received in tablet form imatinib (STI571) 400 mg once daily.	Drug: imatinib mesylate; imatinib mesylate was supplied in 100 and 400 mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free Survival up to 60 Months	Recurrence-free survival assessment is based on the radiologic evidence and is defined as the time from the date of first dose of imatinib to the date of the first documented disease recurrence or death due to any cause (event).	Baseline up to 60 months
Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months	Recurrence-free survival (RFS) assessment is based on the radiologic evidence and is defined as the time from the date of first dose of imatinib to the date of the first documented disease recurrence or death due to any cause (event). RFS estimates were summarized using the Kaplan-Meier product-limit method (Kaplan 1958). Censoring rules for RFS with the earliest occurring rule used in the analysis: subjects without objective recurrence of disease who were alive at the time of their discontinuation from study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment and subjects recording antineoplastic therapy during the study were censored on the date of the therapy initiated	Baseline up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) at 60 Months	Overall survival was defined as the time from the date of the first dose of study drug to the date of death. Subjects who were alive at the time of discontinuation/completion of the study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment. Full analysis set.	Baseline up to approximately 60 months
Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months	Overall survival was defined as the time from the date of the first dose of study drug to the date of death. Subjects who were alive at the time of discontinuation/completion of the study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment. Full analysis set.	Baseline up to appoximately 60 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Raut CP, Espat NJ, Maki RG, Araujo DM, Trent J, Williams TF, Purkayastha DD, DeMatteo RP. Efficacy and Tolerability of 5-Year Adjuvant Imatinib Treatment for Patients With Resected Intermediate- or High-Risk Primary Gastrointestinal Stromal Tumor: The PERSIST-5 Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e184060. doi: 10.1001/jamaoncol.2018.4060. Epub 2018 Dec 13.
• Essat M, Cooper K. Imatinib as adjuvant therapy for gastrointestinal stromal tumors: a systematic review. Int J Cancer. 2011 May 1;128(9):2202-14. doi: 10.1002/ijc.25827.

Helpful Links

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2009
• Primary Completion (Actual): December 20, 2016
• Study Completion (Actual): December 20, 2016

Study Registration Dates

• First Submitted: March 20, 2009
• First Submitted That Met QC Criteria: March 20, 2009
• First Posted (Estimate): March 23, 2009

Study Record Updates

• Last Update Posted (Actual): March 14, 2018
• Last Update Submitted That Met QC Criteria: March 9, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Gastrointestinal Diseases; Digestive System Diseases; Adjuvant; Imatinib; Gastrointestinal Neoplasms; Digestive System Neoplasms; Protein Kinase Inhibitors; Gastrointestinal Stromal Tumors; PERSIST; PERSIS-5
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: CSTI571BUS282