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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Nov 2014 → ongoing

Decision date (initial)

2024-10-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-512243-23-00

EudraCT number

2014-000898-39

ClinicalTrials.gov

NCT02413736

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Calculate the recurrence-free survival (RFS) after randomisation

Secondary objectives 4

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

Conditions and MedDRA coding

gastrointestinal stromal tumor

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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 tumour recurrence following surgery and 3 years of adjuvant imatinib defined as one of the following: 1) gastric GIST with mitotic count >10/50 HPFs HPF, 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 rupture is defined by spillage of the tumour contents into the abdominal cavity. A core 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 from a 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.

Exclusion criteria 15

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 38 months.
6. Neoadjuvant imatinib for a duration that exceeds 12 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 one of the following: basal cell skin cancer, a cervical carcinoma in situ, a small (2 cm or less in diameter) node-negative breast cancer (pT1N0M0), a low Gleason score (<8) local (T1 or T2) prostate cancer. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Recurrence-free survival (RFS). 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 endpoints 4

1. Overall survival.
2. GIST-specific survival. 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. Safety.
4. Quality of Life

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Mikael Eriksson

Public contact point

Organisation

Region Skane

Contact name

Mikael Eriksson

Third parties 6

Locations

8 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications