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.

• Register: EUCTR
• Last refreshed on: 1 February 2016
• Main ID: EUCTR2014-000898-39-FI
• Date of registration: 04/11/2014
• Prospective Registration: Yes
• Primary sponsor: Scandinavian Sarcoma Group
• Public title: 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.
• Scientific title: Three versus five years of adjuvant imatinib as treatment of patients with operable GIST with a high risk for recurrence: A randomised phase III study.
• Date of first enrolment: 19/11/2014
• Target sample size: 300
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000898-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Belgium, Denmark, Finland, Germany, Italy, Netherlands, Norway, Poland, Spain, Sweden, United Kingdom

Contacts

• Name: SSG secretariat
• Affiliation: Scandinavian Sarcoma Group

• Name: SSG secretariat
• Affiliation: Scandinavian Sarcoma Group

Key inclusion & exclusion criteria

Inclusion criteria:
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, or
2) non-gastric GIST with mitotic count >5/50 HPFs, or
3) tumour rupture
Tumour rupture (spillage of the tumour contents into the abdominal cavity) may have occurred either before or at surgery.
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

Exclusion criteria:
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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

gastrointestinal stromal tumor (GIST)

Intervention(s)

Trade Name: Glivec
Product Name: Glivec
Product Code: STI571
Pharmaceutical Form: Tablet

Primary Outcome(s)

Secondary Objective: 1. Calculate the overall survival
2. Calculate the GIST-specific survival
3. Assess the toxicity in patients treated with imatinib
4. Assess the Quality of life in patients treated with imatinib

Main Objective: Calculate the recurrence-free survival (RFS) after randomisation

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(s)

Secondary end point(s): 1. Overall survival
2. GIST-specific survival
3. Safety
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.
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.
3. Common Terminology Criteria for Adverse Events [CTCAE] version 3.0 collected every 3 months from randomisation
4. Quality of Life (EQ-5D instrument) collected every 3 months from randomisation

Secondary ID(s)

SSGXXII

Source(s) of Monetary Support

Novartis Pharma