Gastrointestinal Stromal Tumor (GIST)
Conditions
Keywords
Imatinib, Protein Kinase Inhibitors, Gastrointestinal Stromal Tumors, Digestive System Diseases, Digestive System Neoplasms, Gastrointestinal Diseases, Gastrointestinal Neoplasms, Adjuvant, PERSIST, PERSIS-5
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.
Interventions
DRUGimatinib mesylate
imatinib mesylate was supplied in 100 and 400 mg tablets
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-free Survival up to 60 Months | Baseline 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 | Baseline 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) at 60 Months | Baseline up to approximately 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 | Baseline up to appoximately 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. |
Countries
United States
Participant flow
Pre-assignment details
Total of 113 subjects were screened and 91 were enrolled..
Participants by arm
| Arm | Count |
|---|---|
| Imatinib All subjects received in tablet form imatinib (STI571) 400 mg once daily. | 91 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Post Treatment After Survival Follow-up | Administrative problems | 4 |
| Post Treatment After Survival Follow-up | Death | 1 |
| Post Treatment After Survival Follow-up | Lost to Follow-up | 5 |
| Post Treatment After Survival Follow-up | Withdrawal by Subject | 1 |
| Treatment Period | Administrative problems | 1 |
| Treatment Period | Adverse Event | 15 |
| Treatment Period | Death | 2 |
| Treatment Period | Disease progression/relapse | 1 |
| Treatment Period | Lost to Follow-up | 3 |
| Treatment Period | Protocol Violation | 4 |
| Treatment Period | Withdrawal by Subject | 19 |
Baseline characteristics
| Characteristic | Imatinib |
|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 12.64 |
| ECOG Status ECOG = 0 | 59 Participants |
| ECOG Status ECOG = 1 | 32 Participants |
| Primary lesion location Abdomen | 1 participant |
| Primary lesion location Abdominal; Proximal Jejunal | 1 participant |
| Primary lesion location Duodenum | 4 participant |
| Primary lesion location Exact Location In Small Bowel Not Identified | 1 participant |
| Primary lesion location Gastric | 50 participant |
| Primary lesion location Gastric Serosa-Min Invasion Outer Musc Prop | 1 participant |
| Primary lesion location Ileum And Cecum | 1 participant |
| Primary lesion location Jejunum ileum | 21 participant |
| Primary lesion location Other | 15 participant |
| Primary lesion location Pelvis - Organ Of Origin Unknown | 1 participant |
| Primary lesion location Recto Vaginal | 1 participant |
| Primary lesion location Rectum | 1 participant |
| Primary lesion location Retroperitoneal Mass | 1 participant |
| Primary lesion location Sigmoid Colon | 1 participant |
| Primary lesion location Small Bowel | 6 participant |
| Sex: Female, Male Female | 43 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 91 / 91 |
| serious Total, serious adverse events | 28 / 91 |
Outcome results
Primary
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
Time frame: Baseline up to 60 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imatinib | Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months | 12 months | 97.7 percentage of patients |
| Imatinib | Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months | 18 months | 97.7 percentage of patients |
| Imatinib | Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months | 24 months | 96.5 percentage of patients |
| Imatinib | Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months | 36 months | 95.1 percentage of patients |
| Imatinib | Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months | 48 months | 95.1 percentage of patients |
| Imatinib | Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months | 60 months | 90.1 percentage of patients |
Primary
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).
Time frame: Baseline up to 60 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imatinib | Recurrence-free Survival up to 60 Months | Subject with an event | 9 participants with an event |
| Imatinib | Recurrence-free Survival up to 60 Months | Event = disease recurrence | 7 participants with an event |
| Imatinib | Recurrence-free Survival up to 60 Months | Event=death | 2 participants with an event |
| Imatinib | Recurrence-free Survival up to 60 Months | Subjects censored | 82 participants with an event |
Secondary
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.
Time frame: Baseline up to appoximately 60 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imatinib | Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months | 18 months | 100.00 percentage of participants |
| Imatinib | Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months | 12 months | 100.00 percentage of participants |
| Imatinib | Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months | 24 months | 98.0 percentage of participants |
| Imatinib | Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months | 36 months | 98.0 percentage of participants |
| Imatinib | Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months | 48 months | 98.0 percentage of participants |
| Imatinib | Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months | 60 months | 93.8 percentage of participants |
Secondary
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.
Time frame: Baseline up to approximately 60 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imatinib | Overall Survival (OS) at 60 Months | subjects who died | 3 participants |
| Imatinib | Overall Survival (OS) at 60 Months | subjects censored | 88 participants |