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Pigmented Villonodular SynovitisPhase 2NCT01261429

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

A Phase 2 study testing Tasigna in people with Pigmented Villonodular Synovitis, run by Centre Leon Berard at 15 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pigmented Villonodular Synovitis
What is being tested?
Tasigna
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
15 sitesin 5 countries
Study dates
Dec 2010to Apr 2013
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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)

Who cannot join

  • 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
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  • 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

Trial locations and contacts

15 sites in 5 countries.

15 sites in 5 countries

France8 sites

  • Institut Bergonié

    Bordeaux

  • Centre Oscar Lambret

    Lille

  • Centre Léon Bérard

    Lyon

  • Hôpital La Timone

    Marseille

  • Institut Paoli Calmettes

    Marseille

  • Institut Curie

    Paris

  • Institut Claudius Regaud

    Toulouse

  • Institut Gustave Roussy

    Villejuif

Other trials in France

Italy2 sites

  • Istituto Nazionale dei Tumori

    Milan

  • Regina Elena National Cancer Institute

    Roma

Other trials in Italy

Netherlands2 sites

  • Leiden University Medical Center

    Leiden

  • Radboud University Nijmegen Medical Centre

    Nijmegen

Other trials in Netherlands

United Kingdom2 sites

  • University College Hospital UCL Hospitals NHS Foundation Trust

    London

  • Oxford Cancer Centre

    Oxford

Other trials in United Kingdom

Poland1 site

  • Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

    Warsaw

Other trials in Poland

About this study

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.

Read more

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

Read the detailed description

A key secondary objective of the study will be to determine the efficacy of 24 weeks (6 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 key secondary objective was defined for the purpose of a further analysis (not described in this protocol) which will pool the data of the PVNS study with those of a similar concomitant study conducted in the US and Australia.

The other secondary objectives will be:

To evaluate the efficacy of nilotinib according to:

  • The objective tumour response rate (Complete response + Partial Response according to RECIST version 1.1) after 12 weeks of treatment
  • The duration of treatment response
  • The best overall response obtained during the study
  • The progression-free survival (PFS)
  • The time to progression (TTP)
  • The time to treatment failure (TTF)
  • The proportion of patients with an operable tumour after nilotinib exposure according to investigator evaluation
  • The description of concomitant treatments use
  • The correlation between trough levels of nilotinib and objective tumour response To assess the safety of nilotinib for PVNS/TGCT patients

An exploratory objective of the study will be to study the relationship between the objective tumour response and the following tumour characteristics (tissues collected in a prior surgery, or by biopsy, upon specific acceptance by the patient; if no tissue is available in the prior surgery, a biopsy will be done at visit 2):

Presence of COL6A3/CSF1 fusion gene Presence of M-CSF, CSF1R, KIT, PDGFRA and B on immunohistochemistry Presence of phosphorylated c-fms on tumour samples Activation of the PI3K/Akt/mTor pathway, presence of activating mutations of ras, and other potential molecular alterations

Being tested
Tasigna
Keywords
Pigmented villonodular synovitis, tenosynovial giant cell tumour, nilotinib
Medical subject headings
Synovitis, Pigmented Villonodular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TasignaDrug

    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.

Study groups in NCT01261429
Study groupRoleWhat they receive
NilotinibExperimentalNot described
Receives: Drug: Tasigna

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: after 12 weeks (3 months) of treatment

Secondary outcomes (12)

  1. 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).

    Measured: after 24 weeks (6 months) of treatment

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

    Measured: after 12 weeks of treatment

  3. Duration of response

    Measured: during the study

  4. Best overall response

    Measured: during the study

  5. Progression-free survival

    Measured: during the study

  6. Time to progression

    Measured: during the study

  7. Time to treatment failure

    Measured: during the study

  8. 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)

    Measured: after 12 weeks of treatment

  9. Proportion of patients with an operable tumour after nilotinib exposure according to investigator evaluation

    Measured: at the end of the study (last visit)

  10. Concomitant treatment use during the study

    Measured: during the study

  11. Correlation between trough level of nilotinib at 6 weeks and 12 weeks and objective tumour response

    Measured: at the end of the study

  12. 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.

    Measured: at the end of the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2010 (estimated)
  2. Study startDec 2010
  3. Primary completionApr 2013
  4. Study completionApr 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01261429
Sponsor's protocol ID
PVNS
Other IDs
2010-018869-29
Status last verified
Apr 2013
First submitted
15 Dec 2010
Last updated
16 Apr 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 17148989

  • 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.

    PubMed 10671695

  • 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.

    PubMed 16407111

  • 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.

    PubMed 17527089

  • 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.

    PubMed 15637141

  • 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.

    PubMed 18296418

  • 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.

    PubMed 17851554

  • 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

  • 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.

    PubMed 35932628

  • 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.

    PubMed 29571946

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tasigna in people with Pigmented Villonodular Synovitis, run by Centre Leon Berard at 15 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in France, Italy, Netherlands, United Kingdom, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: after 12 weeks (3 months) of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01261429, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2013.

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