Study of Nilotinib Efficacy in Pigmented Villo-Nodular Synovitis/ Tenosynovial Giant Cell Tumour (PVNS/TGCT)

NCT01261429 | Completed Phase 2 DMC

• 2 other identifiers: PVNS2010-018869-29
• Study Type: interventional
• Target: 50
• Locations: 5 countries
• Sites: 15

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. 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

Conditions

Pigmented Villonodular Synovitis

Keywords

Pigmented villonodular synovitis; tenosynovial giant cell tumour; nilotinib

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (12)

• 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

• Objective tumour response according to RECIST version 1.1 (CR and PR) after 12 weeks of treatment

  after 12 weeks of treatment

• Duration of response

  during the study

• Best overall response

  during the study

• Progression-free survival

  during the study

Study Arms (1)

Nilotinib

EXPERIMENTAL

Drug: Tasigna

Interventions

Tasigna DRUG

The study drug is nilotinib (Tasigna®). All patients will be administered with nilotinib 400 mg twice a day for one year. The patient will begin the treatment the day of inclusion. The prescribed dose should be swallowed whole with a glass of water. Doses of 400 mg should be administered twice daily approximately 12 hours apart. Patients should not eat within two hours before and one hour after taking nilotinib and need to avoid foods such as grapefruit juice which may inhibit CYP3A4 enzymes.

Nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Centre Leon Berard: lead
• Ministry of Health, France: collaborator

Study Sites (15)

Institut Bergonié

Bordeaux, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Hôpital La Timone

Marseille, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Institut Curie

Paris, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Istituto Nazionale dei Tumori

Milan, Italy

Location

Regina Elena National Cancer Institute

Roma, Italy

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands

Location

Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, Poland

Location

University College Hospital UCL Hospitals NHS Foundation Trust

London, United Kingdom

Location

Oxford Cancer Centre

Oxford, United Kingdom

Location

Related Publications (11)

• 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. doi: 10.1097/01.coc.0000239142.48188.f6.

  PMID: 17148989 BACKGROUND

• 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.

  PMID: 10671695 BACKGROUND

• 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. doi: 10.1073/pnas.0507321103. Epub 2006 Jan 6.

  PMID: 16407111 BACKGROUND

• 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. doi: 10.1097/PAS.0b013e31802b86f8.

  PMID: 17527089 BACKGROUND

• 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. doi: 10.1182/blood-2004-10-3967. Epub 2005 Jan 6.

  PMID: 15637141 BACKGROUND

• 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. No abstract available.

  PMID: 18296418 BACKGROUND

• 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. doi: 10.1038/sj.leu.2404944. Epub 2007 Sep 13. No abstract available.

  PMID: 17851554 BACKGROUND

• 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

  BACKGROUND

• 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

  BACKGROUND

• Spierenburg G, Grimison P, Chevreau C, Stacchiotti S, Piperno-Neumann S, Le Cesne A, Ferraresi V, Italiano A, Duffaud F, Penel N, Metzger S, Chabaud S, van der Heijden L, Perol D, van de Sande MAJ, Blay JY, Gelderblom H. Long-term follow-up of nilotinib in patients with advanced tenosynovial giant cell tumours: Long-term follow-up of nilotinib in TGCT. Eur J Cancer. 2022 Sep;173:219-228. doi: 10.1016/j.ejca.2022.06.028. Epub 2022 Aug 3.

  PMID: 35932628 DERIVED

• Gelderblom H, Cropet C, Chevreau C, Boyle R, Tattersall M, Stacchiotti S, Italiano A, Piperno-Neumann S, Le Cesne A, Ferraresi V, Penel N, Duffaud F, Cassier P, Toulmonde M, Casali P, Taieb S, Guillemaut S, Metzger S, Perol D, Blay JY. Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2018 May;19(5):639-648. doi: 10.1016/S1470-2045(18)30143-8. Epub 2018 Mar 20.

  PMID: 29571946 DERIVED

MeSH Terms

Conditions

Synovitis, Pigmented Villonodular

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Giant Cell Tumor of Tendon Sheath; Giant Cell Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Synovitis; Joint Diseases; Musculoskeletal Diseases; Tendinopathy; Muscular Diseases

Study Officials

• Jean Yves Blay, PR

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 15, 2010
• First Posted: December 16, 2010
• Study Start: December 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: April 16, 2013

Record last verified: 2013-04

Locations

PL (1); GB (2); FR (8); IT (2); NL (2)