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A randomized, open-label, multi-center study to evaluate the efficacy of nilotinib versus best supportive care with or without a tyrosine kinase inhibitor (investigator's choice) in adult patients with gastrointestinal stromal tumors resistant to both imatinib and sunitinib.

Phase 3
Completed
Conditions
GIST
10017991
Registration Number
NL-OMON30672
Lead Sponsor
ovartis
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
10
Inclusion Criteria

Amendment 1
* Age * 18 years
* Histologically confirmed diagnosis of GIST that is unresectable and/or metastatic and therefore not amenable to surgery or combined modality with curative intent
* Radiological confirmation of disease progression during imatinib therapy at a dose at least 400 mg daily and radiological confirmation of disease progression during sunitinib therapy that was started at 50 mg daily dose OR documented intolerance to imatinib or sunitib, is defined as patients who discontinued imatinib or sunitinib due to any * Grade 3 adverse events that cannot be managed by appropriate supportive care or medical intervention or persist after dose reduction In addition any * grade 2 Adverse event that persist * 1 month in spite of dose interruption and optimal supportive care.
* At least one measurable site of disease (RECIST) a Visit 2
* WHO Performance Status of 0, 1 or 2 at Visit 1 and Visit 2
* Patients must have normal organ, electrolytes, and marrow function at Visit 1 and Visit 2
See also Amendment 1 page 17 - section 2.8 for changes

Exclusion Criteria

Amendment 1
* Prior treatment with nilotinib or any other tyrosine kinase inhibitors other than imatinib or sunitinib.
* 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
* Prior or concomitant malignancies
* Impaired cardiac function at Visit 1 or 2 (LVEF < 45% ), significant impaired conduction of the heart, use of a cardiac pacemaker, congenital long QT syndrome, history of or presence of significant ventricular or atrial tachyarrhythmias or clinically significant resting bradycardia (< 50bpm), QTc > 450 msec, right bundle branch block plus left anterio hemiblock, bifascicular block, myocardial infarction within 12 months prior to Visit 1, unstable angina diagnosed or treated during the past 12 months prior to Visit 1, other clinically significant heart disease
* Patients with severe and/or uncontrolled concurrent medical disease that could cause unacceptable safety risks or compromise compliance with the protocol
* Use of therapeutic coumarin derivatives
* Use of any medications that prolong the QT interval and CYP3A4 inhibitors
* Patients who are pregnant or breast feeding
See also Amendment 1 page 17 section 2.9 for detail on changes

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Primary endpoints<br /><br>* Progression free survival (PFS)</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>Secondary endpoints<br /><br>* Response, time-to response, and overall survival<br /><br>* Safety and tolerability</p><br>
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