Clinical trial NCT00867113: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-03-23
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

   -

Primary outcomes:
measure: Recurrence-free Survival up to 60 Months
timeFrame: Baseline up to 60 months
measure: Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months
timeFrame: Baseline up to 60 months
Secondary outcomes:
measure: Overall Survival (OS) at 60 Months
timeFrame: Baseline up to approximately 60 months
measure: Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months
timeFrame: Baseline up to appoximately 60 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego - Moores Cancer Center Moores UCSD Cancer Center (31)
state: California
city: Aurora
country: United States
facility: University of Colorado University of Colorado
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center Department of Medical Oncology
state: District of Columbia
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Gainesville
country: United States
facility: Longstreet Cancer Center
state: Georgia
city: Coeur d'Alene
country: United States
facility: Kootenai Medical Center Kootenai Cancer Cancer
state: Idaho
city: Evanston
country: United States
facility: North Shore University Health System
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute Dana-Farber
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute Karmonos Cancer Instit. (40)
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine Center for Advanced Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Southern Nevada Cancer Research Foundation S. Nevada Cancer Res (2)
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering (7)
state: New York
city: Durham
country: United States
facility: Duke University Medical Center Duke University Med Ctr (8)
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University OHS University
state: Oregon
city: Hershey
country: United States
facility: Penn State University / Milton S. Hershey Medical Center Penn Stat University
state: Pennsylvania
city: Providence
country: United States
facility: Roger Williams Medical Center Medical Center
state: Rhode Island
city: Kingsport
country: United States
facility: Kingport Hematology Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (4)
state: Texas
city: San Antonio
country: United States
facility: South Texas Oncology and Hematology, PA South Texas Onc/Hem
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates Viriginia Oncology Assoc.
state: Virginia
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.
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.