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).

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

Age * 18 years
At least one measurable site of disease on CT/MRI scan as defined by RECIST criteria
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
- have 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.
WHO Performance Status of 0, 1 or 2
Patients must have normal organ, electrolyte, and marrow function

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
Prior malignancies 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 metastasis
Major surgery within 4 weeks prior to randomization or who have not recovered from prior surgery.
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.
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.
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.
Patients actively receiving therapy with herbal medicines that are CYP3A4 inhibitors and/or inducers, and treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome), except for gastrectomy.
History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
Acute or chronic uncontrolled liver, or severe renal disease considered unrelated to disease.
Patients who have received wide field radiotherapy within 4 weeks or limited field radiation for palliation within 2 weeks prior to randomization or who have not recovered from side effects of such therapy

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary efficacy variable is progression free survival.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The key secondary efficacy variables include disease control rate (DCR), time<br /><br>to treatment failure (TTF) and overall survival (OS).</p><br>

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