Pigmented Villonodular Synovitis Clinical Trial
Official title:
Phase II Study of Nilotinib Efficacy in Pigmented Villo-Nodular Synovitis/ Tenosynovial Giant Cell Tumour (PVNS/TGCT)
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.
The primary objective of the study will be to determine the efficacy of 12 weeks (3 months)
of nilotinib treatment as measured by the non progression rate (Complete response + Partial
Response + Stable disease according to Response Evaluation Criteria In Solid Tumours -
RECIST version 1.1) in patients with progressive or relapsing PVNS/TGCT who cannot be
treated by surgery.
this study is an international, multicentre, non-randomized, open-label phase II clinical
trial with a Bayesian design.
A maximum sample size of 50 patients will be included in the study
Status | Completed |
Enrollment | 50 |
Est. completion date | April 2013 |
Est. primary completion date | April 2013 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Age > 18 years - Histologically confirmed diagnosis of inoperable progressive or relapsing PVNS/TGCT OR resectable tumour requesting mutilating surgery - Demonstrated progressive disease in the last 12 months - At least one measurable site of disease on MRI/CT scan according to RECIST criteria (RECIST version 1.1) based on investigator's assessment - WHO Performance status of 0, 1 or 2 - Adequate organ, electrolyte and marrow function, defined as the following: serum bilirubin > or =1.5 x ULN, ALT and AST < or = 2.5 x ULN, serum creatinine < or = 1.5 x ULN or creatinine clearance > or = 50 mL/min, absolute neutrophil count (ANC) > or = 1.5x109/L, platelets > or = 100x109/L, serum lipase < or =1.5 x ULN, magnesium = lower limit of normal (LLN) and potassium = LLN - 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) - Signed written informed consent form - Covered by a medical insurance (in countries where applicable) Exclusion Criteria: - 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 - Known hypersensitivity to nilotinib or to any of the excipients, galactose intolerance, lactase deficiency or glucose-galactose malabsorption prior to enrollment - Acute or chronic uncontrolled liver disease, or severe renal disease - 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) - Patient with family history of long QT syndrome, of unexplained syncope or of unexplained sudden death - 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 - History of non-compliance to medical regimens - 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) - Concomitant treatment with warfarin - 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) - Prior treatment with imatinib except if no progression was demonstrated |
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
France | Institut Bergonié | Bordeaux | |
France | Centre Oscar Lambret | Lille | |
France | Centre Léon Bérard | Lyon | |
France | Hôpital La Timone | Marseille | |
France | Institut Paoli Calmettes | Marseille | |
France | Institut Curie | Paris | |
France | Institut Claudius Regaud | Toulouse | |
France | Institut Gustave Roussy | Villejuif | |
Italy | Istituto Nazionale dei Tumori | Milano | |
Italy | Regina Elena National Cancer Institute | Roma | |
Netherlands | Leiden University Medical Center | Leiden | |
Netherlands | Radboud University Nijmegen Medical Centre | Nijmegen | |
Poland | Sklodowska-Curie Memorial Cancer Center and Institute of Oncology | Warsaw | |
United Kingdom | University College Hospital UCL Hospitals NHS Foundation Trust | London | |
United Kingdom | Oxford Cancer Centre | Oxford |
Lead Sponsor | Collaborator |
---|---|
Centre Leon Berard | Ministry of Health, France |
France, Italy, Netherlands, Poland, United Kingdom,
Blay JY, El Sayadi H, Thiesse P, Garret J, Ray-Coquard I. Complete response to imatinib in relapsing pigmented villonodular synovitis/tenosynovial giant cell tumor (PVNS/TGCT). Ann Oncol. 2008 Apr;19(4):821-2. doi: 10.1093/annonc/mdn033. Epub 2008 Feb 21. — View Citation
Brownlow N, Russell AE, Saravanapavan H, Wiesmann M, Murray JM, Manley PW, Dibb NJ. Comparison of nilotinib and imatinib inhibition of FMS receptor signaling, macrophage production and osteoclastogenesis. Leukemia. 2008 Mar;22(3):649-52. Epub 2007 Sep 13. — View Citation
Cupp JS, Miller MA, Montgomery KD, Nielsen TO, O'Connell JX, Huntsman D, van de Rijn M, Gilks CB, West RB. Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides. Am J Surg Pathol. 2007 Jun;31(6):970-6. — View Citation
Dewar AL, Cambareri AC, Zannettino AC, Miller BL, Doherty KV, Hughes TP, Lyons AB. Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib. Blood. 2005 Apr 15;105(8):3127-32. Epub 2005 Jan 6. — View Citation
Martin RC 2nd, Osborne DL, Edwards MJ, Wrightson W, McMasters KM. Giant cell tumor of tendon sheath, tenosynovial giant cell tumor, and pigmented villonodular synovitis: defining the presentation, surgical therapy and recurrence. Oncol Rep. 2000 Mar-Apr;7(2):413-9. Review. — View Citation
Mendenhall WM, Mendenhall CM, Reith JD, Scarborough MT, Gibbs CP, Mendenhall NP. Pigmented villonodular synovitis. Am J Clin Oncol. 2006 Dec;29(6):548-50. Review. — View Citation
P. A. Cassier, S. Stacchiotti, H. Gelderblom, D. M. Thomas, W. Van Der Graaf, B. M. Seddon, D. Julien, A. J. Wagner, J. Blay. Imatinib mesylate for the treatment of locally advanced and/or metastatic pigmented villonodular synovitis/tenosynovial giant cell tumor (PVNS/TGCT). J Clin Oncol. 2010 (suppl; abstr 10012); 28:15s. Meeting: 2010 ASCO Annual Meeting Abstract No: 10012
V. Ravi, W. Wang, D. M. Araujo, J. A. Ludwig, R. J. Luke, V. O. Lewis, J. C. Trent, R. S. Benjamin, S. Patel. Imatinib in the treatment of tenosynovial giant-cell tumor and pigmented villonodular synovitis. J Clin Oncol. 2010 (suppl; abstr 10011); 28:15s. Meeting: 2010 ASCO Annual Meeting Abstract No: 10011
West RB, Rubin BP, Miller MA, Subramanian S, Kaygusuz G, Montgomery K, Zhu S, Marinelli RJ, De Luca A, Downs-Kelly E, Goldblum JR, Corless CL, Brown PO, Gilks CB, Nielsen TO, Huntsman D, van de Rijn M. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):690-5. Epub 2006 Jan 6. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | after 12 weeks (3 months) of treatment | No | |
Secondary | 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). | after 24 weeks (6 months) of treatment | No | |
Secondary | Objective tumour response according to RECIST version 1.1 (CR and PR) after 12 weeks of treatment | after 12 weeks of treatment | No | |
Secondary | Duration of response | during the study | No | |
Secondary | Best overall response | during the study | No | |
Secondary | Progression-free survival | during the study | No | |
Secondary | Time to progression | during the study | No | |
Secondary | Time to treatment failure | during the study | No | |
Secondary | 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) | after 12 weeks of treatment | No | |
Secondary | Proportion of patients with an operable tumour after nilotinib exposure according to investigator evaluation | at the end of the study (last visit) | No | |
Secondary | Concomitant treatment use during the study | during the study | No | |
Secondary | Correlation between trough level of nilotinib at 6 weeks and 12 weeks and objective tumour response | at the end of the study | No | |
Secondary | Safety evaluation will be based on overall safety profile characterized by type, frequency and severity (as graded using NCI-CTCAE V3.0) of adverse events. | at the end of the study | Yes |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT01207492 -
Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor
|
Phase 2 | |
Terminated |
NCT04938180 -
A Phase 2 Study of Intravenous AMB-05X in Tenosynovial Giant Cell Tumor Patients
|
Phase 2 | |
Active, not recruiting |
NCT05059262 -
Study of Vimseltinib for Tenosynovial Giant Cell Tumor
|
Phase 3 | |
Active, not recruiting |
NCT04731675 -
An Open-Label Study of Intra-articular AMB-05X Injections in Subjects With Tenosynovial Giant Cell Tumor of the Knee
|
Phase 2 | |
Completed |
NCT02371369 -
Phase 3 Study of Pexidartinib for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS)
|
Phase 3 | |
Completed |
NCT02471716 -
Study of Cabiralizumab in Patients With Pigmented Villonodular Synovitis / Diffuse Type Tenosynovial Giant Cell Tumor
|
Phase 1/Phase 2 | |
Recruiting |
NCT05349643 -
A Study to Evaluate Safety and Efficacy of AMB-05X Injections in Subjects With TGCT
|
Phase 2 | |
Completed |
NCT04952896 -
Clinical Study of Magnetic Resonance Imaging and Deep Learning of Joint Synovial Disease
|
||
Active, not recruiting |
NCT03069469 -
Study of Vimseltinib (DCC-3014) in Patients With Advanced Tumors and Tenosynovial Giant Cell Tumor
|
Phase 1/Phase 2 | |
Completed |
NCT04955535 -
Screening of Specific Genes for Pigmented Villous Nodular Synovitis
|
||
Active, not recruiting |
NCT05804045 -
Study of Pimicotinib (ABSK021) for Tenosynovial Giant Cell Tumor (MANEUVER)
|
Phase 3 | |
Completed |
NCT01643850 -
MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)
|
Phase 2 |