A randomized, open-label, multi-center study to evaluate the efficacy of nilotinib versus imatinib in adult patients with gastrointestinal stromal tumors resistant to imatinib and resistant/intolerant to sunitinib - ND

• Conditions: Gastrointestinal stromal tumors (GIST); MedDRA version: 9.1Level: LLTClassification code 10051066Term: Gastrointestinal stromal tumour

• Registration Number: EUCTR2006-002267-11-IT
• Lead Sponsor: OVARTIS FARMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-11-07
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 210

Inclusion Criteria

Age >=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 2, as defined by RECIST criteria (see Post Text Suppl 3 for details) WHO Performance Status of 0, 1 or 2 at Visit 1 and Visit 2 Patients must have normal organ, electrolyte, and marrow function at Visit 1 and Visit 2 as defined below: 1. Absolute Neutrophil Count (ANC) >=1.5-1.0 x 10 alla nona/L; 2. Platelets >=100 x 10 alla nona/L; 3. ALT and AST <= 2.5 x upper limit of normal (ULN) or <= 5.0 x ULN if considered due to tumor; 4. Alkaline phosphatase <= 2.5 x ULN unless considered due to tumor; 5. Serum bilirubin <= 1.5 x ULN; 6. Serum lipase and amylase <= 1.5 x ULN; 7. Serum potassium >= lower limit of normal (LLN) or correctable to within normal limits with supplements by Visit 2 8. Total calcium ≥ LLN or correctable to within normal limits with supplements by Visit Serum magnesium >=LLN or correctable to within normal limits with supplements by Visit 2 10. Serum phosphorous >= LLN or correctable to within normal limits with supplements by Visit 2 11. Serum creatinine <= 1.5 x ULN or 24-hour creatinine clearance >= 50 ml/min. Ability to understand and willingness to sign a written informed consent
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) yes
F.1.3.1 Number of subjects for this age range

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 requiring active treatment) other than GIST with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ Impaired cardiac function at Visit 1 or 2, including any one of the following: 1. LVEF < 45% or below the institutional LLN range (whichever is higher) as determined by MUGA scan or echocardiogram at Visit 1 2. Complete left bundle branch block 3. Use of a cardiac pacemaker 4. ST depression of > 1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads 5. Congenital long QT syndrome 6. History of or presence of significant ventricular or atrial tachyarrhythmias 7. Clinically significant resting bradycardia (< 50 beats per minute) 8. QTc > 450 msec on screening ECG (using the QTcF formula) 9. Right bundle branch block plus left anterior hemiblock, bifascicular block 10. Myocardial infarction within 12 months prior to Visit 1 11. Unstable angina diagnosed or treated during the past 12 months prior to Visit 1 12. Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) 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. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs, uncontrolled diabetes For patients who undergo PET 1. Inability to remain laying down in PET scanner for up to one hour 2. Absence of at least one metastatic lesion greater than or equal to 2 cm on pre-dose CT scan or other radiographic imaging as defined by RECIST criteria Use of therapeutic coumarin derivatives (i.e. warfarin, acenoucumarol, phenprocoumon) Use of any medications that prolong the QT interval and CYP3A4 inhibitors if 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/medicalpros/ drug-lists/printable-drug-list.cfm for a comprehensive list of agents that prolong the QT interval as well as Post-Text Supplement 2. Patients who have undergone major surgery <= 2 weeks prior to Visit 1 or who have not recovered from side effects of such surgery 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 A history of noncompliance to medical regimens or inability or unwillingness to return for scheduled visits Patients who are pregnant, breast feeding or women of childbearing potential (WOCBP). Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential Women of reproductive potential ,to include female partners of heterosexual or bisexual patients, must agree to use an effective method o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate whether the efficacy of nilotinib is superior to imatinib as measured by progression free survival;Secondary Objective: 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;Primary end point(s): Progression free survival (PFS)