| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| GIST (Gastrointestinal stromal tumor) is a rare disease affecting 15 patients per 1 million individuals and comprising 5% of all sarcomas. Mutations in the genes of KIT or PDGFRA lead to constitutive activation of the encoded receptor and are the pathogenetic reason for the development of clinical GIST. GIST is a potentially curable disease, if complete resection of localized tumor is possible. Inoperable GIST cannot be cured at present. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10051066 |
| E.1.2 | Term | Gastrointestinal stromal tumour |
|
| 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 |
| Efficacy of dasatinib treatment as assessed by fusion PET/CT-scan |
|
| E.2.2 | Secondary objectives of the trial |
Efficacy and safety of dasatinib in GIST
To correlate efficacy of dasatinib with KIT and PDGRF mutation status
To correlate efficacy and safety with dasatinib drug exposure
Efficacy of second-line treatment with another TK-inhibitor
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Patient has histologically proven diagnosis of GIST
• Positive PET/CT with [18F]-fluorodeoxyglucose uptake of the target lesion(s), performed within 2 weeks prior to registration. Imaging data have been transmitted in DICOM format to the CHUV.
•Patient must have measurable disease by conventional scans (CT or MRI) performed within 2 weeks prior to registration. Imaging data have been stored on a CD-ROM in DICOM format.
•WHO performance status 0-2
•Age ≥ 18 years
•Adequate hematological values: hemoglobin ≥ 90 g/l (this may be achieved by transfusion if needed); neutrophils ≥ 1.5 x 109/l; platelets ≥100 x 109/l.
•Adequate hepatic function: bilirubin ≤ 2 x ULN; AP ≤ 2.5 x ULN; ASAT and/or ALAT ≤ 2.5 x ULN.
•Women are not breastfeeding, are using contraception if sexually active and of childbearing potential, are not pregnant and agree not to become pregnant during participation in the trial or during the 12 months thereafter. A negative pregnancy test before inclusion into the trial is required for all women < 50 years (unless considered unnecessary by the investigator).
Men agree not to father a child during participation in the trial or during the 12 months thereafter and use effective contraception method.
•Patient’s condition, compliance and geographic proximity allow proper staging, complete treatment and follow-up.
•Patient must give written informed consent before registration |
|
| E.4 | Principal exclusion criteria |
• Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
•Previous therapy against GIST (particularly tyrosine kinase inhibitors at any time)
•Concurrent treatment with other experimental drugs or other anticancer therapy, treatment in a clinical trial within 30 days prior to trial entry
•Signs or history of CNS metastases
•Hypocalcemia: serum Ca++ ≤ LLN
•Clinically significant cardiovascular disease, including uncontrolled hypertension, congestive heart failure within 6 months prior to registration, QTc > 450 msec or major conduction abnormality (unless a cardiac pacemaker is present).
•Concurrent medical condition which could impair the ability of the patient (at the judgment of the investigator) to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes) or which may increase the risk of toxicity, including:
a) pleural or pericardial effusion of any grade
b) clinically significant coagulation or platelet function disorder (e.g. known
von Willebrand’s disease)
c) infection requiring intravenous antibiotics
d) ongoing significant gastrointestinal bleeding
e) nausea, vomiting or malabsorption syndrome which could interfere with ingestion
or absorption of oral drug
•Known hypersensitivity to trial drug
•Any concomitant drugs contraindicated for use with the trial drug according to the dasatinib investigator’s brochure[45].
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Response as assessed by fusion PET/CT scan according to EORTC PET Study Group criteria at 4 weeks compared to baseline |
|
| 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 | Yes |
| 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 | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 3 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
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