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

Primary Purpose

Gastrointestinal Stromal Tumor (GIST)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
imatinib mesylate
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastrointestinal Stromal Tumor (GIST) focused on measuring Imatinib, Protein Kinase Inhibitors, Gastrointestinal Stromal Tumors, Digestive System Diseases, Digestive System Neoplasms, Gastrointestinal Diseases, Gastrointestinal Neoplasms, Adjuvant, PERSIST, PERSIS-5

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

    -

Sites / Locations

  • University of California San Diego - Moores Cancer Center Moores UCSD Cancer Center (31)
  • University of Colorado University of Colorado
  • Washington Hospital Center Department of Medical Oncology
  • University Cancer & Blood Center, LLC
  • Longstreet Cancer Center
  • Kootenai Medical Center Kootenai Cancer Cancer
  • North Shore University Health System
  • Dana Farber Cancer Institute Dana-Farber
  • Karmanos Cancer Institute Karmonos Cancer Instit. (40)
  • Washington University School of Medicine Center for Advanced Medicine
  • Southern Nevada Cancer Research Foundation S. Nevada Cancer Res (2)
  • Dartmouth Hitchcock Medical Center
  • Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering (7)
  • Duke University Medical Center Duke University Med Ctr (8)
  • Oregon Health & Science University OHS University
  • Penn State University / Milton S. Hershey Medical Center Penn Stat University
  • Roger Williams Medical Center Medical Center
  • Kingport Hematology Oncology
  • MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (4)
  • South Texas Oncology and Hematology, PA South Texas Onc/Hem
  • Virginia Oncology Associates Viriginia Oncology Assoc.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Imatinib

Arm Description

All subjects received in tablet form imatinib (STI571) 400 mg once daily.

Outcomes

Primary Outcome Measures

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).
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

Secondary Outcome Measures

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.
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.

Full Information

First Posted
March 20, 2009
Last Updated
March 9, 2018
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00867113
Brief Title
Five Year Adjuvant Imatinib Mesylate (Gleevec®) in Gastrointestinal Stromal Tumor (GIST)
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
July 22, 2009 (Actual)
Primary Completion Date
December 20, 2016 (Actual)
Study Completion Date
December 20, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Stromal Tumor (GIST)
Keywords
Imatinib, Protein Kinase Inhibitors, Gastrointestinal Stromal Tumors, Digestive System Diseases, Digestive System Neoplasms, Gastrointestinal Diseases, Gastrointestinal Neoplasms, Adjuvant, PERSIST, PERSIS-5

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
91 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Imatinib
Arm Type
Experimental
Arm Description
All subjects received in tablet form imatinib (STI571) 400 mg once daily.
Intervention Type
Drug
Intervention Name(s)
imatinib mesylate
Intervention Description
imatinib mesylate was supplied in 100 and 400 mg tablets
Primary Outcome Measure Information:
Title
Recurrence-free Survival up to 60 Months
Description
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).
Time Frame
Baseline up to 60 months
Title
Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months
Description
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
Time Frame
Baseline up to 60 months
Secondary Outcome Measure Information:
Title
Overall Survival (OS) at 60 Months
Description
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.
Time Frame
Baseline up to approximately 60 months
Title
Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months
Description
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.
Time Frame
Baseline up to appoximately 60 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients 18 years of age or older. Patient must have had a histological diagnosis of primary GIST. The tumor must expressed KIT (CD117) protein by immunohistochemistry performed by central pathology. 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 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. 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. Performance status 0 or 1 (ECOG) 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 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. 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. Written, voluntary informed consent. Exclusion Criteria: Patient has metastatic GIST to the peritoneum, liver, lymph node, or other sites or recurrent GIST. Prior treatment for GIST with the exception of prior treatment with imatinib adjuvant lasting ≤ 8 weeks following gross surgical resection. Patient has received any other investigational agents within 28 days of first day of study drug dosing. 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) 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). Patient has a known diagnosis of human immunodeficiency virus (HIV) infection. Patient receiving concurrent treatment with warfarin (acceptable alternative: low-molecular weight heparin). Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent. -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Diego - Moores Cancer Center Moores UCSD Cancer Center (31)
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
University of Colorado University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Washington Hospital Center Department of Medical Oncology
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University Cancer & Blood Center, LLC
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
Longstreet Cancer Center
City
Gainesville
State/Province
Georgia
ZIP/Postal Code
30501
Country
United States
Facility Name
Kootenai Medical Center Kootenai Cancer Cancer
City
Coeur d'Alene
State/Province
Idaho
ZIP/Postal Code
83814
Country
United States
Facility Name
North Shore University Health System
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Dana Farber Cancer Institute Dana-Farber
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Karmanos Cancer Institute Karmonos Cancer Instit. (40)
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Washington University School of Medicine Center for Advanced Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Southern Nevada Cancer Research Foundation S. Nevada Cancer Res (2)
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering (7)
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Duke University Medical Center Duke University Med Ctr (8)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Oregon Health & Science University OHS University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Penn State University / Milton S. Hershey Medical Center Penn Stat University
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033-0850
Country
United States
Facility Name
Roger Williams Medical Center Medical Center
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02908
Country
United States
Facility Name
Kingport Hematology Oncology
City
Kingsport
State/Province
Tennessee
ZIP/Postal Code
37660
Country
United States
Facility Name
MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (4)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
South Texas Oncology and Hematology, PA South Texas Onc/Hem
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78259
Country
United States
Facility Name
Virginia Oncology Associates Viriginia Oncology Assoc.
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30383140
Citation
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.
Results Reference
derived
PubMed Identifier
21387287
Citation
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.
Results Reference
derived
Links:
URL
http://www.novartisclinicaltrials.com/webapp/etrials/searchTrial.do?t=i&trialID=747&keywords=CSTI571BUS282
Description
Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Learn more about this trial

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

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