metastatic or unresectable gastrointestinal stromal tumor in patients resistant to imatinib or sunitinib MedDRA version: 14.0 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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. • 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
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the preliminary efficacy of nilotinib in pretreated patients with unresectable or metastatic gastrointestinal stromal tumors. Efficacy is defined as stable disease (SD), partial response (PR) or complete response (CR) during the first 4 months according to RECIST criteria.;Secondary Objective: • To evaluate the time to response (SD, PR or CR) based on RECIST criteria. • To evaluate the time to tumor progression based on RECIST criteria. • To evaluate duration of response based on RECIST criteria. • To evaluate progression free survival (PFS) during the first 4 months based on RECIST criteria of the patients who were included due to an intolerability of a prior treatment. • 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 efficacy variable of this study will be the rate of patients showing complete response (CR), partial response (PR) or stable disease (SD) during the first four months according to RECIST criteria. The primary efficacy variable will be analyzed using the ITT and per protocol populations. Local tumor assessment data will be used. | — |
Countries
Germany, Italy, United Kingdom
Outcome results
None listed