Three or five years of adjuvant imatinib for the treatment of patients with operable GIST with a high risk of relapse: A randomized phase III study.
PURPOSE OF THE STUDY
Three years of imatinib is considered the standard duration of post therapy for patients with operable high-risk GIST. Yet, many patients are still at a high risk of GIST recurrence after completion of three years of adjuvant imatinib, and might benefit from further adjuvant imatinib therapy. The aim of SSGXXII is to compare the effect of giving imatinib for 5 years against 3 years, in patients who have undergone surgery for GIST, with the intent to prevent the tumour from coming back. The trial will look at the effect of the efficacy and safety of 5 years of treatment compared to 3 years.
- Male/Female aged >= 18 years.
- Morphological and immunohistological documentation of GIST
- Macroscopically complete surgical resection of GIST (either R0 or R1 resection).
- Mutation analysis of KIT and PDGFR genes has been carried out.
- A high risk of GIST recurrence
- Eastern Cooperative Oncology Group performance status <= 2.
- Adequate organ function.
- Female patients of childbearing potential must have a negative pregnancy test within 14 days before initiation of study drug dosing. Postmenopausal women must have amenorrhea for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
- Patient willing to be followed up at the study site regardless of the result of randomization.
- Patient has provided a written, voluntary informed consent prior to study-specific screening procedures.
- Presence of distant metastases or local recurrence of GIST.
- Not willing to donate tumor tissue and/or blood samples for the study molecular studies.
- Presence of a substitution mutation at PDGFRA codon D842 (usually D842V).
- Administration of adjuvant imatinib longer than for 3 years is planned regardless of the result of randomization, or “life long” imatinib administration is planned.
- Prior adjuvant (+ neoadjuvant) therapy with imatinib mesylate for at least 35 months has not been completed, or the total duration of prior adjuvant (+ neoadjuvant) imatinib administration exceeds the total duration of 38 months.
- Neoadjuvant imatinib for a duration that exceeds 12 months.
- Longer than 4-week break during adjuvant imatinib administration.
- The dose of imatinib at completion of 3 years of adjuvant imatinib was 200 mg per day or less or greater than 800 mg per day.
- Patient has received any investigational anti-cancer agents during adjuvant imatinib or between completion of adjuvant imatinib and the date of randomization.
- Patient has been free of another malignancy for less than 5 years except if the other malignancy is not currently clinically significant nor requiring active intervention, or if the other malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Recent existence of any other malignant disease is not allowed.
- Patient with Grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., congestive heart failure, myocardial infarction within 6 months of study entry).
- Female patients who are pregnant or breast-feeding.
- Severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, severe chronic renal disease, or active uncontrolled infection).
- Known diagnosis of human immunodeficiency virus (HIV) infection.
- Patient with a significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
- Inability or difficulty in swallowing tablets.
- Patients with chronic or active hepatitis B.
DETAILED INFORMATION AVAILABLE
Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) please click here.
Professor John Zalcberg AO
Associate Professor Sumitra Ananda
MRFF International Clinical Trial Collaborations 2020