A randomized, open-label, multi-center phase III study to evaluate the efficacy and safety of nilotinib versus imatinib in adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) and its Protocol extension (see PTS#1) - ND
- Conditions
- Adult patients with histologically confirmed unresectable or metastatic GIST, either who have not received prior therapy with TKIs or, who experienced recurrence of GIST = 6 months after stopping adjuvant treatment with imatinib.MedDRA version: 9.1Level: LLTClassification code 10062427Term: Gastrointestinal stromal tumor
- Registration Number
- EUCTR2008-004758-34-IT
- Lead Sponsor
- OVARTIS FARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 736
Age ≥ 18 years At least one measurable site of disease on CT/MRI scan as defined by RECIST criteria (refer to Post-text supplement 2) based on investigator?s assessment - Histologically confirmed diagnosis of GIST which is unresectable and/or metastatic and either: have not received prior therapy with Imatinib or any investigational therapies (for example, sunitinib or any other TKIs). Note: newly diagnosed patients may have received up to 14 days imatinib treatment for disease management while awaiting study start. have recurrent GIST ≥ 6 months after stopping adjuvant treatment with imatinib and have subsequently not received any other investigational therapies (for example, sunitinib or any other TKIs). For patients with recurrent GIST after stopping adjuvant imatinib two CT scans will be required prior to study entry: one demonstrating absence of disease following completion of adjuvant imatinib and another demonstrating recurrence of disease ≥ 6 months after discontinuation of adjuvant imatinib. WHO Performance Status of 0, 1 or 2 Patients must have normal organ, electrolyte, and marrow function as defined below Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L ALT and AST ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if considered due to tumor Alkaline phosphatase ≤ 2.5 x ULN unless considered due to tumor Serum bilirubin ≤ 1.5 x ULN Serum lipase and amylase ≤ 1.5 x ULN Serum potassium within the normal limits or corrected to within normal limits with supplements Total calcium (corrected for serum albumin) within the normal limits or corrected to within normal limits with supplements Serum magnesium within the normal limits or corrected to within normal limits with supplements Serum phosphorous within the normal limits or corrected to within normal limits with supplements Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min (calculated creatinine clearance using Cockroft formula is acceptable) A written informed consent must be obtained.
Protocol extension:
- Demonstrated disease progression (as per RECIST criteria) under the assigned treatment in the core part of the study Signed Informed Consent for the extension part of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Prior treatment with nilotinib or any other TKIs or targeted agents with the exception of adjuvant imatinib or, for patients with newly diagnosed metastatic/unresectable GIST whose disease requires therapy while awaiting study start, up to 14 days of treatment with imatinib (a washout period of 4 days will be required prior to the first dose of study medication). Patients who experience disease progression during adjuvant therapy with imatinib Prior or concomitant malignancies (except if the other primary malignancy is neither currently clinically significant or requiring active intervention) other than GIST with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ Impaired cardiac function, including any one of the following: LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher) as determined by echocardiogram or MUGA scan. Inability to determine the QT interval on ECG. Complete left bundle branch block. Use of a ventricular-paced pacemaker. Congenital long QT syndrome or a known family history of long QT syndrome. History of or presence of clinically significant ventricular or atrial tachyarrhythmias. Clinically significant resting bradycardia (< 50 beats per minute). QTc > 450 msec (using the QTcF formula) as determined by central reading. If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc. History or signs of prior myocardial infarction. History of unstable angina (during the last 12 months). Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension). Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. uncontrolled diabetes, active or uncontrolled infection. History of significant congenital or acquired bleeding disorder unrelated to cancer. Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery. History of non-compliance to medical regimens or inability to grant consent. Use of therapeutic coumarin derivatives (i.e. warfarin, acenoucumarol, phenprocoumon). Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug administration. Please see http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm or http://www.arizonacert.org/medical-pros/drug-lists/drug-lists for a list of agents that prolong the QT interval. This list may not be comprehensive.
Protocol extension:
Use of other anticancer treatments or investigational drugs (with exception of the study drugs) Withdrawal of the main Informed Consent for the core part of the study History of noncompliance with study drug treatment in the core part of the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method