metastatic or unresectable gastrointestinal stromal tumor MedDRA version: 20.0 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor System Organ Class: 100000004864
Conditions
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
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 • At least one measurable site of disease on CT/MRI scan at Visit 1, as defined by RECIST criteria (see Post Text Suppl 3 for details) The scans should be at maximum 2 weeks old. New scans are only required as baseline scans if they are older then approx. 2 weeks. • WHO Performance Status of 0, 1 or 2 • Patients must 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.): 1. Potassium = LLN, 2. Magnesium = LLN, 3. Phosphorus = LLN, 4. Total calcium (corrected for serum albumin) = LLN • Patients must have normal organ, electrolyte, and marrow function as defined below: 1. Absolute Neutrophil Count (ANC) = 1.5x 109/L; 2. Platelets = 100 x 109/L; 3. ALT and AST = 2.5 x upper limit of normal (ULN) or = 5.0 x ULN if considered due to tumor; 4. Alkaline phosphatase = 2.5 x ULN unless considered due to tumor; 5. Serum bilirubin = 1.5 x ULN; 6. Serum lipase and amylase = 1.5 x ULN; 7. Serum creatinine = 1.5 x ULN or 24-hour creatinine clearance = 50 ml/min. (calculated creatinine clearance using Cockroft formula is acceptable) 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
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 with the exception of imatinib targeted therapy as an adjuvant therapy or imatinib in first line treatment for a maximum of 4 weeks • 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 including any one of the following: 1. LVEF 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. 8. Right bundle branch block plus left anterior hemiblock, bifascicular block 9. Myocardial infarction within 12 months prior to Visit 1 10. 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 • Patients who are pregnant, breast feeding or women of childbearing potential (WOCBP). Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential Women of reproductive potential ,to include female partners of heterosexual or bisexual patients, must agree to use an effective method of contraception during the study and for up to three months following termination of the study. • Patients unwilling or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of Nilotinib in patients with unresectable or metastatic gastrointestinal stromal tumors. Efficacy is defined as the proportion of patients showing stable disease (SD), partial response (PR) or complete response (CR) during the first 6 months according to RECIST criteria.;Secondary Objective: •To evaluate the objective tumor response rate based on RECIST criteria (complete response (CR) and partial response PR) •To evaluate time to overall response (PR or CR) •To evaluate duration of response •To evaluate progression free survival (PFS) during the first 6 months using RECIST criteria •To evaluate overall survival (OS) •To evaluate the safety and tolerability of Nilotinib as measured by rate and severity of adverse events •To evaluate the population pharmacokinetics of Nilotinib ;Primary end point(s): The primary variable is defined as the best response at month 6 determined according to the RECIST criteria based on local radiological assessments. | — |
Countries
Finland, France, Germany, Italy, Spain
Outcome results
None listed