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

• Conditions: metastatic or unresectable gastrointestinal stromal tumor in patients resistant to imatinib or sunitinib; MedDRA version: 14.0Level: LLTClassification code 10062427Term: Gastrointestinal stromal tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2008-000357-35-DE
• Lead Sponsor: ovartis Pharma GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-08-28
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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.
•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; (if considered due to tumor = 2.5 x ULN)
- Serum lipase and amylase = 1.5 x ULN; (if considered due to tumor = 2.5 x ULN)
•Serum creatinine = 1.5 x ULN or 24-hour creatinine clearance = 50 ml/min (calculated creatinine clearance using Cockroft formula is acceptable).
•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.
•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).
•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/medical-pros/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.
•Female patients who are pregnant or breast feeding or patients of reproductive potential not employing an effective method of birth control.
•Patients unwilling or unable to comply with the protocol.

Study & Design

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