Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor

Study Overview
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Brief Summary
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Nilotinib is a drug that is used to treat a form of a blood cancer called leukemia. Nilotinib works by blocking the action of a protein that might be important for the growth of pigmented villonodular synovitis (PVNS). In this research study the investigators are testing whether nilotinib can stop the growth of PVNS or improve the symptoms experienced from PVNS.

Detailed Description
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In this research study, each cycle of study drug dosing will last 4 weeks (28 days). During each cycle, participants will take nilotinib by mouth twice daily. During the first cycle, participants will come to the clinic on Days 1 and 8. For Cycles 2-4 and every 3 cycles thereafter, they will come to the clinic on Day 1. The following tests and procedures will be performed at specific time points during study treatment: MRI or CT scans; physical examinations; vital signs; blood work; questionnaires and EKG. Participants may continue in this research study for as long as they do not have serious side effects or their disease does not get worse.

Official Title
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A Multi-Center Single Agent Phase II Study of the Efficacy of Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor

Conditions
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Diffuse-type Giant Cell Tumor, Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor

Intervention / Treatment
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* Drug: nilotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of recurrent PVNS ( or diffuse-type giant cell tumor or tenosynovial giant cell tumor) that is unresectable, metastatic, or for which the patient refuses surgical intervention Progressive disease in the last 12 months, as demonstrated by imaging or clinical appearance of new tumors, in the opinion of the treating investigator At least one site of measurable disease according to RECIST 1.1 on MRI (or CT scan for metastatic disease) Any number or type of prior systemic therapies, with the exception of known or suspected CSF1 receptor inhibitors as outlined in exclusion criteria below 18 years of age or older Life expectancy greater than 6 months ECOG Performance Status of 0, 1 or 2 Normal organ and marrow function as defined in the protocol QTc less than or equal to 450 ms on 12-lead ECG Negative urine or serum pregnancy test within days of start of study drug administration for women of childbearing potential. Women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 3 months following study drug discontinuation Exclusion Criteria: Prior treatment with known or suspected CSF1 receptor inhibitor, including nilotinib, imatinib, sunitinib, or sorafenib, or other approved or investigational tyrosine kinase inhibitors used for treatment of diffuse-type giant cell tumor Concurrent treatment with other investigational agents Inability to tolerate or contraindication to MRI scanning for participants with localized disease Impaired cardiac function Current treatment with strong CYP3A4 inhibitors that cannot either be discontinued or switched to a different medication prior to starting study drug Current treatment with any medications that have the potential to prolong the QT interval and that cannot either be discontinued or switched to a different medication prior to starting study drug Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug Acute or chronic pancreatic disease Acute or chronic liver disease Another primary malignant disease requiring systemic treatment or radiation History of significant congenital or acquired bleeding disorder unrelated to cancer Major surgery within 28 days prior to Day 1 of the study Treatment with other investigational agents within 28 days of day 1 History of non-compliance to medical regimens or inability to grant consent Women who are pregnant or breastfeeding Other comorbidities that would interfere with study participation or safety in the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nilotinib<br>Nilotinib 200 mg taken as 400 mg twice daily, continuously | Drug: nilotinib<br>* Taken orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Progression Free Survival | To estimate progression free survival at 6 months in participants with recurrent PVNS treated with nilotinib. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Tumor Response Rate (OR) | To determine overall tumor response rate [% complete response (CR) + % partial response (PR) by RECIST 1.1]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR) is a disappearance of all target lesions. Partial Response (PR) is a >=30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR. | 2 years | 
| Clinical Benefit Rate | To determine the clinical benefit rate [% CR + % PR + % stable disease by RECIST 1.1] at 6 months. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR) is a disappearance of all target lesions. Partial Response (PR) is a >=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nilotinib