Further 2 years of adjuvant imatinib may improve recurrence-free survival (RFS) of patients who are at a high risk of GIST recurrence despite completion of 3 years of adjuvant imatinib.
- Conditions
- gastrointestinal stromal tumor (GIST)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-000898-39-AT
- Lead Sponsor
- Scandinavian Sarcoma Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 300
1. Age = 18 years.
2. Morphological and immunohistological documentation of GIST (immunostaining for KIT [CD117] and/or DOG-1 positive, or mutation of KIT or PDGFRA present in tumour tissue).
3. Macroscopically complete surgical resection of GIST (either R0 or R1 resection).
4. Mutation analysis of KIT and PDGFR genes has been carried out.
5. A high risk of GIST recurrence, either
1) gastric GIST with mitotic count >10/50 HPFs high Power field of the microscope) or >10/5mm2, or
2) non-gastric GIST with mitotic count >5/50 HPFs, or >5/5 HPFs mm2, or
3) non-gastric GIST treated with neoadjuvant imatinib and initially larger than 10 cm, or
4) tumour rupture
Tumour rupture may have occurred before or at surgery. Tumour ruptureis defined by spillage of the tumour contents into the abdominal cavity. Acore needle biopsy from the tumour, or tumour bleed with no apparent spillage of the tumour contents, are not considered ruptures.If only a small amount of pretreatment tumour tissue is available from a core needle biopsy, it is acceptable to multiply the mitotic count obtained from fewer than 50 HPFs to approximate the counts obtained from 50 HPFs in surgical biopsies, or to multiply the count obtained froma tumour tissue area less than 5 mm2 to approximate the counts obtained from the 5 mm2 area. However, if only minimal amount of tumour tissue is available from a core needle biopsy (from 5 or fewer HPFs, or only 1 mitosis can be identified), multiplication should not be attempted and is not considered acceptable. For further explanation of this expanded high risk classification, please see section 3.2.3.
6. ECOG performance status = 2.
7. Adequate organ function, defined as
serum total bilirubin <1.5 x ULN (upper limit of normal), serum AST (SGOT) and ALT (SGPT) <2.5 x ULN, creatinine <1.5 x ULN; blood ANC (neutrophil count) =1.0 x 109/L, platelet count =100 x 109/L.
8. Female patients of childbearing potential must have a negative pregnancy test within 14 days before initiation of study drug dosing. Postmenopausal women must have amenorrhoea 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.
9. Patient willing to be followed up at the study site regardless of the result of randomisation.
10. Patient has provided a written, voluntary informed consent prior to study-specific screening procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150
1. Presence of distant metastases or local recurrence of GIST.
2. Not willing to donate tumour tissue and/or blood samples for the study molecular studies.
3. Presence of a substitution mutation at PDGFRA codon D842 (usually D842V).
4. Administration of adjuvant imatinib longer than for 3 years is planned regardless of the result of randomisation, or life long” imatinib administration is planned.
5. 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 37 months.
6. Neoadjuvant imatinib for a duration that exceeds 9 months.
7. Longer than 4-week break during adjuvant imatinib administration.
8. 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.
9. Patient has received any investigational anti-cancer agents during adjuvant imatinib or between completion of adjuvant imatinib and the date of randomisation.
10. 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.
11. 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).
12. Female patients who are pregnant or breast-feeding.
13. Severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, severe chronic renal disease, or active uncontrolled infection).
14. Known diagnosis of human immunodeficiency virus (HIV) infection.
15. Patient with a significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Calculate the recurrence-free survival (RFS) after randomisation;Secondary Objective: 1. Calculate the overall survival<br>2. Calculate the GIST-specific survival<br>3. Assess the toxicity in patients treated with imatinib<br>4. Assess the Quality of life in patients treated with imatinib;Primary end point(s): Recurrence-free survival (RFS) ;Timepoint(s) of evaluation of this end point: Defined by the time interval between the date of randomisation and the date of first detection of GIST recurrence or death, whichever occurs first. CT/MRI at 6-month intervals during the first 5 years on study in each arm, and then annually.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Overall survival <br>2. GIST-specific survival <br>3. Safety <br>4. Quality of Life;Timepoint(s) of evaluation of this end point: 1. The time period between the date of randomisation and the date of death.<br>2. The time period between the date of randomisation and the date of death considered to be caused by GIST; patients who die from other causes are censored on the date of death.<br>3. Common Terminology Criteria for Adverse Events [CTCAE] version 3.0 collected every 3 months from randomisation<br>4. Quality of Life (EQ-5D instrument) collected every 3 months from randomisation<br>