Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000019808
Ethics application status
Not yet submitted
Date submitted
4/01/2012
Date registered
5/01/2012
Date last updated
21/01/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of the efficacy of nilotinib in the treatment of patients with pigmented villo-nodular synovitis / tenosynovial giant cell tumour
Scientific title
Phase II study of nilotinib efficacy in pigmented villo-nodular synovitis / tenosynovial giant cell tumour (PVNS/TGCT)
Secondary ID [1] 279656 0
NCT01261429 on ClinicalTrials.gov
Universal Trial Number (UTN)
Trial acronym
PVNS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pigmented villo-nodular synovitis 285464 0
Tenosynovial giant cell tumour 285465 0
Condition category
Condition code
Cancer 285647 285647 0 0
Sarcoma (also see 'Bone') - soft tissue

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nilotinib; 2 x 200mg capsule twice daily, orally, for 12 months
Intervention code [1] 283940 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 286203 0
The non-progression rate after 12 weeks (3 months) of
treatment, based on the response evaluated by CT scan or MRI according to RECIST criteria (RECIST
version 1.1) and validated by a central review committee
Timepoint [1] 286203 0
12 weeks
Secondary outcome [1] 295377 0
Non progression rate after 24 weeks (6 months) of treatment, based on the response evaluated
by CT scan or MRI according to RECIST criteria (RECIST version 1.1)
Timepoint [1] 295377 0
24 weeks
Secondary outcome [2] 295378 0
Objective tumour response according to RECIST version 1.1 (CR and PR) after 12 weeks of
treatment
Timepoint [2] 295378 0
12 weeks
Secondary outcome [3] 295379 0
Duration of response, best overall response, progression-free survival, time to progression, time to treatment failure (according to RECIST version 1.1 criteria)
Timepoint [3] 295379 0
During study
Secondary outcome [4] 295380 0
Non progression rate after 12 weeks of treatment, based on the response evaluated locally by
the investigator in charge using CT scan or MRI and according to RECIST criteria (RECIST version
1.1)
Timepoint [4] 295380 0
12 weeks
Secondary outcome [5] 295381 0
Proportion of patients with an operable tumour after nilotinib exposure according to investigator
evaluation
Timepoint [5] 295381 0
End of study
Secondary outcome [6] 295382 0
Concomitant treatment use during the study (determined by clinical assessment)
Timepoint [6] 295382 0
During study
Secondary outcome [7] 295383 0
Correlation between trough level of nilotinib at 6 weeks and 12 weeks and objective tumour response, determined by matching laboratory testing of blood nilotinib levels and investigator evaluation of response
Timepoint [7] 295383 0
End of study

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment outside Australia
Country [1] 4033 0
United Kingdom
State/province [1] 4033 0
Country [2] 4034 0
Netherlands
State/province [2] 4034 0
Country [3] 4035 0
Italy
State/province [3] 4035 0
Country [4] 4036 0
Poland
State/province [4] 4036 0
Country [5] 4037 0
France
State/province [5] 4037 0

Funding & Sponsors
Funding source category [1] 284439 0
Commercial sector/Industry
Name [1] 284439 0
Novartis
Country [1] 284439 0
Australia
Primary sponsor type
Hospital
Name
Centre Leon Berard
Address
28, Rue Laennec
69373 Lyon Cedex 08
Country
France
Secondary sponsor category [1] 283362 0
Other Collaborative groups
Name [1] 283362 0
Australasian Sarcoma Study Group
Address [1] 283362 0
Level 2, Research Division
Peter MacCallum Cancer Centre
St Andrews Place
East Melbourne VIC 3002
Country [1] 283362 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 286417 0
Ethics committee address [1] 286417 0
Ethics committee country [1] 286417 0
Date submitted for ethics approval [1] 286417 0
16/01/2012
Approval date [1] 286417 0
Ethics approval number [1] 286417 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33574 0
Address 33574 0
Country 33574 0
Phone 33574 0
Fax 33574 0
Email 33574 0
Contact person for public queries
Name 16821 0
Gemma Tait
Address 16821 0
Centre for Biostatistics & Clinical Trials
Peter MacCallum Cancer Centre
St Andrews Place
East Melbourne VIC 3002
Country 16821 0
Australia
Phone 16821 0
+61 3 9656 5829
Fax 16821 0
Email 16821 0
gemma.tait@petermac.org
Contact person for scientific queries
Name 7749 0
Gemma Tait
Address 7749 0
Centre for Biostatistics & Clinical Trials
Peter MacCallum Cancer Centre
St Andrews Place
East Melbourne VIC 3002
Country 7749 0
Australia
Phone 7749 0
+61 3 9656 5829
Fax 7749 0
Email 7749 0
gemma.tait@petermac.org

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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