E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastrointestinal stromal tumour (GIST) |
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E.1.1.1 | Medical condition in easily understood language |
Gastrointestinal stromal tumour (GIST) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051066 |
E.1.2 | Term | Gastrointestinal stromal tumour |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to document progression-free survival (PFS) in patients who discontinue imatinib after treatment with imatinib for longer than 5 years for oligo-metastatic GIST (≤ 3 metastases) and who have no detectable overt GIST lesions in CT/MRI imaging following complete surgical resection (R0/R1-resection), radiofrequency ablation (RFA) of the metastases, or following systemic treatment for oligometastatic GIST |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to study overall survival and the quality of life (QoL) in the patients who discontinue imatinib. Data about response to reinstitution of imatinib after GIST progression will be collected from the hospital records from those patients who restarted imatinib after completion of the study.
The exploratory objectives are to study the relationship between study endpoints and circulating biomarkers, relationships between study endpoints and biomarkers in resected tumors prior to study entry, and changes in the blood cell counts and blood biochemistry after stopping imatinib as compared to the baseline values on imatinib, measured at the time of the screening examinations. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18.
2. Morphological and immunohistochemical documentation of GIST (immunostaining for KIT/(CD117) and/or DOG-1 (anoctamin-1)) must be positive on a tumour sample. Patients with demonstrated mutation in KIT or PDGFRA may be entered to the study despite negative immunostaining for KIT and DOG-1 provided that tumour histology is compatible with GIST.
3. >5.0 years of treatment with imatinib for metastatic disease when the breaks in imatinib administration are taken into account.
4. No more than 3 detectable metastases in the liver and/or in the abdomen in imaging of the abdomen and the pelvis during the course of the disease or at surgery.
5. Confirmed metastatic GIST in history by radiology, histology, or both.
6. Macroscopically complete resection of all metastases (either R0 or R1 surgery). Patients who have microscopically infiltrated margins (or suspected microscopical infiltration, R1) are allowed to enter the study. RFA of liver metastasis is allowed in place of surgery. Patients whose oligometastatic disease had disappeared completely so that no remaining target lesion for surgery or RFA can be identified (including absence of residual cyst-like lesions) are allowed to enter the study.
7. Eastern Co-operative Oncology Group (ECOG) performance status ≤ 2.
8. Patient has provided a written, voluntary informed consent prior to study entry and any study-specific procedures. |
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E.4 | Principal exclusion criteria |
1. Patients with metastases outside of the abdomen (e.g. in the bones or lungs).
2. Not willing to donate tumor tissue and/or blood samples for the molecular studies that aim at predicting of GIST recurrence.
3. Presence of an SDH mutation or other evidence for SDH deficiency.
4. Presence of neurofibromatosis-1.
5. R2 resection of the primary tumor or metastasis.
6. Patient with inability to grant reliable informed consent.
7. Inability to comply with the scheduled follow-up.
8. Progressive disease during imatinib or other systemic treatments for GIST, or before or after surgery/RFA of the metastases. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The PFS will be measured from the date of discontinuation of imatinib to the date of first documentation of progression or death (from any cause), whichever occurs first.
1-year PFS in the first 15 patients included. The study is terminated if 10 or more of the 15 patients (≥67 %) have progression of disease or withdraws from the study within the first 12 months from the date of study entry.
The final analysis will be performed when the patients without an event have a median follow-up time of above 36 months |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall survival will be measured from the date of discontinuation of imatinib to the dato of death resulting from any cause.
The final analysis will be performed when the patients without an event have a median follow-up time of above 36 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |