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). - N/A

• Conditions: adult patients with histologically confirmed unresectable or metastatic GIST, either who have not received any prior anti-neoplastic therapy or, who experienced recurrence of GIST > 6 months after stopping adjuvant treatment with imatinib.; MedDRA version: 14.1Level: LLTClassification code 10062427Term: Gastrointestinal stromal tumorSystem Organ Class: 100000004864

• Registration Number: EUCTR2008-004758-34-AT
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11-12
• Last Update Posted: 24 November 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 736

Inclusion Criteria

•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 any prior anti-neoplastic therapy other than adjuvant imatinib. Note: newly diagnosed patients may have received up to 14 days of treatment with imatinib for disease management while awaiting entry to the study
or
•had no clinical or radiological evidence of disease during the adjuvant treatment with imatinib, have recurrent GIST = 6 months after stopping adjuvant treatment with imatinib, and who have subsequently not received any other therapies,
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
•Hemoglobin = 9.0 g/dL
•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 liver metastases
•Alkaline phosphatase = 2.5 x ULN or = 5.0 x ULN if considered due to liver metastases
•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
•A written informed consent must be obtained

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

•Any prior anti-neoplastic therapy (eg TKIs, chemotherapy, investigational therapy) with the exception of patients who have received adjuvant imatinib or patients with newly diagnosed metastatic/unresectable GIST whose disease requires therapy while awaiting entry to the study, up to 14 days of treatment with imatinib (a washout period of a minimum of 4 days will be required prior to the first dose of study medication).
•History of active malignancy (other than GIST) within 10 years prior to study entry 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 (during the last 12 months).
•History of unstable angina (during the last 12 months).
•Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension).
•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.
•Known symptomatic brain metastases.
•Major surgery within 4 weeks prior to randomization or who have not recovered from prior surgery.
•History of non-compliance to medical regimens or inability to grant consent.
•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 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.
•Patients actively receiving therapy with strong CYP3A4 inhibitors and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See Post-text supplement 4 for a list of these medications. This list may not be comprehensive.
•Patients actively receiving therapy with strong CYP3A4 inducers and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See Post-text supplement 4 for a list of these medications.. This list may not be comprehensive.
•Patients actively receiving therapy with herbal medicines that are CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. These herbal medicines may include Echinacea,

Study & Design

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