None listed
Conditions
Brief summary
The purpose of this study is to explore the efficacy of nilotinib as a treatment of patients with progressive or relapsing pigmented villo-nodular synovitis / tenosynovial giant cell tumour (PVNS /TGCT) who cannot be treated by surgery. This study is an international, multicentre, non-randomised, open-label phase II clinical trial with a Bayesian design. Who is it for? You may be eligible for this study if you are aged 18 years and over, have a histologically confirmed diagnosis of inoperable progressive or relapsing PVNS/TGCT OR resectable tumour requesting mutilating surgery, and give your consent to take part. The full inclusion criteria details can be found in the relevant section of this form. Trial details: In this study, you will receive the drug nilotinib in the form of 2 x 200mg capsules twice daily, taken orally over a total period of 12 months. You will also be required to regularly attend clinic for routine tests and assessments.
Interventions
Nilotinib; 2 x 200mg capsule twice daily, orally, for 12 months
Sponsors
Centre Leon Berard
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age >= 18 years 2. Histologically confirmed diagnosis of inoperable progressive or relapsing PVNS/TGCT OR resectable tumour requesting mutilating surgery 3. Demonstrated progressive disease in the last 12 months 4. At least one measurable site of disease on MRI/CT scan according to RECIST criteria (RECIST version 1.1) based on investigator’s assessment 5. WHO Performance status of 0, 1 or 2 6. Adequate organ, electrolyte and marrow function, defined as the following: serum bilirubin <=1.5 x ULN; ALT and AST <=2.5 x ULN; serum creatinine <=1.5 x ULN or creatinine clearance >=50 mL/min; absolute neutrophil count (ANC) >=1.5x10^9/L; platelets >=100x10^9/L; serum lipase <=1.5 x ULN; magnesium = lower limit of normal (LLN) and potassium = LLN 7. Prior adequate physical examination including weight, height, ECOG PS and vital signs (systolic and diastolic blood pressure, heart rate after at least 5 minutes in supine position) 8. Signed written informed consent form
Exclusion criteria
1. Pregnant or lactating female or female of child-bearing potential not employing adequate contraception during the study and for up to three months following termination of the study 2. Known hypersensitivity to nilotinib or to any of the excipients, galactose intolerance, lactase deficiency or glucose-galactose malabsorbtion prior to enrolment 3. Acute or chronic uncontrolled liver disease, or severe renal disease 4. Impaired cardiac function, including: - LVEF<50% or below the institutional lower limit of the normal range (whichever is higher) as determined by echocardiogram or MUGA scan - History or signs of prior myocardial infarction - History of unstable angina - Congenital long QT prolongation - Personal history of unexplained syncope - QTc interval >= 450 msec on screening ECG - Other clinically significant heart disease (e.g. bradycardia, congestive heart failure or uncontrolled hypertension) 5. Patient with family history of long QT syndrome, of unexplained syncope or of unexplained sudden death 6. 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. uncontrolled diabetes, active or uncontrolled infection, history of pancreatitis 7. History of non-compliance to medical regimens 8. Concomitant treatment with medicinal products that induce CYP3A4 (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or St. John’s Wort), or that inhibit the CYP3A4 activity (e.g. ketoconazole, itraconazole, voriconazole, erythromycin, clarithromycin, telithromycin) 9. Concomitant treatment with warfarin 10. Concomitant treatment with anti-arrhythmic drug (e. g. amiodarone, sotalol, disopyramide, quinidine, procainamide) or medication that prolongs the QT interval (e.g. chloroquine, chlorpromazine, domperidone, droperidol, halofantrine, haloperidol, methadone, pentamidine, pimozide, thioridazine) 11. Prior treatment with imatinib except if no progression was demonstrated
Outcome results
None listed