E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastrointestinal stromal tumors (GIST) |
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MedDRA Classification |
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 |
To evaluate whether the efficacy of nilotinib is superior to imatinib as measured by progression free survival |
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E.2.2 | Secondary objectives of the trial |
•To compare the response rate and time to response of nilotinib with imatinib using modified RECIST criteria to assess response
•To compare overall survival of nilotinib with imatinib
•To assess the safety and tolerability of nilotinib as measured by rate and severity of adverse events
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Age : older than 18 years at Visit 1 •Histologically confirmed diagnosis of GIST that is unresectable and/or metastatic and therefore not amenable to surgery or combined modality with curative intent prior to or at Visit 1 •Radiological confirmation of disease progression (CT scan or MRI) during imatinib therapy •Radiological confirmation of disease progression (CT scan or MRI) during sunitinib therapy. For those patients who were intolerant to sunitinib, intolerance (at any dose and/or duration), is defined as patients who did not progress on sunitinib and have discontinued sunitinib therapy due to any ≥ Grade 2 adverse events that persist in spite of optimal supportive care. •At least one measurable site of disease on CT/MRI scan at Visit 1, as defined by RECISTcriteria (see Post Text Suppl 3 for details) •WHO Performance Status of 0, 1 or 2 at Visit 1 and 2 •Patients must have normal organ, electrolyte, and marrow function at Visit 1 and Visit 2 •Ability to understand and willingness to sign a written informed consent
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E.4 | Principal exclusion criteria |
•Prior treatment with nilotinib •Documented intolerance or history of allergy to imatinib •Unable to tolerate imatinib run-in of 7 days minimum •Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks (6 weeks for nitrosurea or mitomycin C) prior to Visit 1 with the exception of imatinib and sunitinib targeted therapy •Prior or concomitant malignancies (with a relapse in the last 5 years or receiving active treatment) other than GIST with the exception of previous or concomitant basal cell skin cancer or previous cervical carcinoma in situ •Impaired cardiac function at Visit 1or 2 •Use of therapeutic coumarin derivatives •Patients who are currently receiving treatment with medications that have the potential to prolong the QT interval •Patients who have undergone major surgery ≤ 2 weeks prior to Visit 1 or who have not recovered from side effects of such therapy Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation < 2 weeks prior to Visit 1 or who have not recovered from side effects of such therapy
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS) |
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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 | Yes |
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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Patients who disease progress on the imatinib arm will be allowed to crossover to the nilotinib arm. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
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 |
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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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The cut-off date for the final primary analysis of progression free survival will be when 136 progression free survival events have occured or alternatively when the last remaining patient drops out, progress or completes a minimum of 32 weeks of dosing, whichever comes first. |
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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 | |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |