Nilotinib in Patients With Relapsed or Metastatic Pigmented Villonodular Synovitis/Tenosynovial Giant Cell Tumor/Diffuse-Type Giant Cell Tumor
Condition: Pigmented Villonodular Synovitis; Diffuse-type Giant Cell Tumor; Tenosynovial Giant Cell Tumor
MeSH terms: Neoplasms; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Synovitis, Pigmented Villonodular; Synovitis
Intervention: nilotinib
Intervention description: Taken orally twice daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: nilotinib

Summary:

      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.
    

Eligibility criteria:

        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