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

Conditions: gastrointestinal stromal tumors
MedDRA version: 12.1Level: LLTClassification code 10051066Term: Gastrointestinal stromal tumour

Registration Number: EUCTR2008-000357-35-IT

Lead Sponsor: OVARTIS FARMA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 206

Inclusion Criteria

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 prior to or at Visit 1. Radiologically confirmed disease progression during imatinib therapy at a dose of at least 400 mg daily and/or radiologically confirmed disease progression during sunitinib therapy OR documented intolerance (defined above in population) to imatinib and/or sunitinib. (Patients with prior additional investigational treatment of GIST prior to study entry can be included.) At least one measurable site of disease on CT/MRI as defined by RECIST criteria (see Post Text Supplement 3 for details). The scans should not be older than approximately 2 weeks. New scans are only required as baseline scans if they are older than approximately 2 weeks. WHO Performance Status of 0, 1 or 2. Patients should have the following laboratory values (≥ LLN (lower limit of normal) or corrected to within normal limits with supplements prior to the first dose of study medication): - Potassium ≥ LLN, - Magnesium ≥ LLN, - Phosphorus ≥ LLN, Total calcium (corrected for serum albumin) ≥ LLN.
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. Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks (6 weeks for nitrosurea or mitomycin C) prior to Visit 1. Prior or concomitant malignancies 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 any one of the following: - LVEF < 45% or below the institutional LLN range (whichever is higher) as determined by echocardiogram at Visit 1. - Complete left bundle branch block. - Use of a ventricular paced cardiac pacemaker. - Congenital long QT syndrome or family history of long QT syndrome. - History of or presence of significant ventricular or atrial tachyarrhythmias. - Clinically significant resting bradycardia (< 50 beats per minute). - QTc > 450 msec on screening ECG (using the QTcF formula). If QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc. - Right bundle branch block plus left anterior hemiblock, bifascicular block. - Myocardial infarction within 12 months prior to Visit 1. - Other clinically significant heart disease (e.g., unstable angina, 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. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs, uncontrolled diabetes. Use of therapeutic coumarin derivatives (i.e. warfarin, acenoucumarol, phenprocoumon). 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.