localized gastrointestinal stromal tumors (GIST) MedDRA version: 13.1 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tasigna 200 mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentra
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 yrs. 2. Histologically documented diagnosis of GIST. KIT-negative tumors morphologically compatible with GIST may be entered provided that the tumors contain either KIT or PDGFRa mutation(s). 3. Local disease (i.e. disease without distant metastases and/or peritoneal/intra-abdominal spread), completely excised through adequate surgery (R0 or R1 resection). 4. WHO Performance status 0, 1 or 2. 5. Patients with >20% of risk of recurrence, according to Miettinen classification (low and very low risk GIST are not eligible): a. The final patient selection criteria will be based on anatomical site, size, mitotic index and tumor rupture. Eligible patients will have: b. tumors > 5 cm with > 5 mitoses/50 high power fields c. tumors > 10 cm d. tumors with > 10 mitoses/50 high power fields e. non-gastric tumors of 2-5 cm with > 5mitoses/50 high power fields f. tumors of 5-10 cm of non-gastric origin g. tumor rupture. 6. Patients have received imatinib (400 mg) for at least 12 months (a maximum 3 months time interval is allowed between the last date of imatinib administration and the first date of nilotinib administration). Imatinib dosing up to 600 mg/d, based on individual imatinib plasma levels, are allowed and/or patients have received imatinib at lower doses (300-400 mg) and showed intolerance to the drug. 7. Multiple surgical interventions are allowed, as long as the disease was inadequately excised before definitive surgery or there was a true local relapse. 8. Adequate end organ function as defined by: a. Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous radiation therapy for GIST, chemotherapy for GIST or molecular treatment for GIST other than imatinib. 2. Impaired cardiac function including any one of the following: a. LVEF 450 msec at baseline ECG (using the QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc j. History or clinical signs of myocardial infarction within 1 year of study entry. k. History of unstable angina within 1 year of study entry. l. Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension). 3. 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, uncontrolled infection). 4. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis. 5. Acute or chronic liver, pancreatic, or severe renal disease considered unrelated to study disease. 6. History of significant congenital or acquired bleeding disorder unrelated to cancer. 7. History of other active malignancy within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ. 8. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. 9. 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, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John’s Wort, and Ginkgo. 10. 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. (Please see http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm for a list of agents that prolong the QT interval.) 11. 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, small bowel resection or gastric bypass surgery). 12. Women who are pregnant, breast feeding or adults of reproductive potential not employing an effective method of birth control. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective method of contraception during the study and for up to three months follo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the activity of nilotinib in patients with localized GIST who have undergone R0 or R1 resection and who have been treated with imatinib for at least 12 months in an adjuvant setting.;Secondary Objective: • To assess the activity of nilotinib at 24 months. The secondary efficacy endpoint is defined as the proportion of patients recurrence-free at month 24. • To assess time to recurrence (TTR) at 12 and 24 months, respectively. TTR is defined as the time from start of treatment to the date of event defined as the first documented recurrence or death due to underlying cancer (GIST). • To assess disease-free survival (DFS) at 12 and 24 months, respectively. DFS is defined as the time from date of start of treatment to the date of event defined as the first documented recurrence or death from any cause. • To assess time to treatment failure (TTF) at 12 and 24 months, respectively. • To assess 5-years overall survival (OS). OS is defined as the time from first study drug administration to death from any cause. • To assess the safety and tolerability of nilotinib. ;Primary end point(s): The primary variable is defined as the proportion of patients recurrence-free at Month 12 based on RECIST criteria. | — |
Countries
Germany
Outcome results
None listed