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

Phase 2
18 Years
Not Enrolling
Pigmented Villonodular Synovitis

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Trial Information

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

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

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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.

Outcome Time Frame:

after 12 weeks (3 months) of treatment

Safety Issue:


Principal Investigator

Jean Yves Blay, PR

Investigator Role:

Principal Investigator

Investigator Affiliation:

Centre Léon Bérard, Lyon


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

December 2010

Completion Date:

April 2013

Related Keywords:

  • Pigmented Villonodular Synovitis
  • Pigmented villonodular synovitis
  • tenosynovial giant cell tumour
  • nilotinib
  • Giant Cell Tumors
  • Synovitis
  • Synovitis, Pigmented Villonodular