E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastrointestinal stromal tumors (GIST) are mesenchymal neoplasms usually arising from the gastrointestinal wall. Pathologically,they present with spindle cells in most cases. Immunohistochemically, GIST cells are almost always positive for CD117.CD117 corresponds to the KIT receptor, a tyrosine kinase receptor which is altered in GIST due to a mutation to the c-kit oncogene. This event is held to be critical for GIST pathogenesis. |
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E.1.1.1 | Medical condition in easily understood language |
Gastrointestinal stromal tumors (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 | 14.1 |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess whether Imatinib mesylate, as an adjunct to complete surgery, is able to improve prognosis of patients with intermediate and high-risk, localized GIST. |
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E.2.2 | Secondary objectives of the trial |
To assess whether there is a difference in relapse-free survival and relapse-free interval between intermediate and high-risk localized GIST patients undergoing complete surgery alone and those undergoing complete surgery plus adjuvant Imatinib mesylate 400 mg daily for two years.
To assess safety of Imatinib mesylate given as an adjuvant to complete surgery in intermediate-risk and high-risk local GIST patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
♦ Histologically proven diagnosis of GIST, with positive immunostaining for KIT (CD117) ♦ Risk of relapse documented on the surgical specimen, according to the 2002 Consensus Approach to Diagnosis of GIST (See Appendix H and Ref. 7), as falling within the “high-risk” category (tumor size >10 cm; or mitotic rate >10/50HPF; or tumor size >5 cm & mitotic rate >5/50HPF) or the “intermediate-risk” category (tumor size <5 cm & mitotic rate 6-10/50HPF; or tumor size 5-10 cm & mitotic rate <5/50HPF). ♦ Surgery performed from 2 weeks to 3 months before randomization (patients randomized in the treated arm should start Imatinib mesylate within 3 months of surgery). ♦ Non evidence of residual macroscopic disease after surgery. Patients with R0 or R1 resection are eligible. ♦ Prior surgery is admitted provided it was devoid of eradicative intent (e.g., surgery with a main diagnostic intent, emergency surgery with a symptomatic intent, etc.) ♦ No prior radiation therapy, no prior chemotherapy for GIST, no prior therapy with Imatinib mesylate, or any other molecular targeted or biological therapy. ♦ Absence of distant metastases, including absence of any peritoneal lesion not contiguous to the primary tumor, while regional positive lymph nodes are admitted provided they have been macroscopically excised. ♦ Age >18 yrs. ♦ WHO PS = 0-2 (see Appendix B) ♦ The cardiac ejection function will be assessed at baseline. The choice of the method is left to physician’s discretion (LVEF (MUGA or ECHO), NT-proBNP….). An ECG must also be performed. No Class 3/4 cardiac problems, as defined by the New York Heart Association Criteria (e.g., congestive heart failure, myocardial infarction within 2 months of study; see Appendix C) ♦ Absence of severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal disease, uncontrolled liver disease, including chronic viral hepatitis, judged at risk of reactivation, uncontrolled active infection, such as HIV infection, etc.). ♦ No prior, or ongoing other malignancy, except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or adequately treated cancer with eradicative intent for which the patient has been continuously disease-free for >5 years. ♦ No ongoing pregnancy or nursing. Women/men of reproductive potential must agree to use an effective contraceptive method throughout the treatment period and for up to 3 months following discontinuation of the drug. Women of reproductive potential must have a negative pregnancy test within 7 days prior to treatment start. |
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E.4 | Principal exclusion criteria | |
E.5 End points |
E.5.1 | Primary end point(s) |
Imatinib monotherapy failure free survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessed at follow-up visits. Patients in treatment arm will be followed every week for the first month, then every 2 weeks for the second month, then monthly until the end of the 6th month of therapy, and subsequently every 3 months until treatment discontinuation. Patients in the control arm and patients in the treatment arm who have completed treatment are followed every 3 months until 2 years from randomization have elapsed, then every 4 months until 5 years have elapsed, and thereafter at least annually, at the discretion of the responsible physician. |
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E.5.2 | Secondary end point(s) |
1) Relapse-free survival; 2) Relapse-free interval; 3) Overall survival; 4) Adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessed at follow-up visits. Patients in treatment arm will be followed every week for the first month, then every 2 weeks for the second month, then monthly until the end of the 6th month of therapy, and subsequently every 3 months until treatment discontinuation. Patients in the control arm and patients in the treatment arm who have completed treatment are followed every 3 months until 2 years from randomization have elapsed, then every 4 months until 5 years have elapsed, and thereafter at least annually, at the discretion of the responsible physician. |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 | Information not present in EudraCT |
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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End of study occurs when all of the following criteria have been satisfied: 1. Thirty days after all patients have stopped protocol treatment 2. The trial is mature for the analysis of the primary endpoint as defined in the protocol 3. The database has been fully cleaned and frozen for this analysis |
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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 | 12 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 12 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |