Phase 3 Study of Pexidartinib for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS)

Not Recruiting

Trial ID: NCT02371369


This is a Phase 3 clinical study, which aims to evaluate the effectiveness of an investigational drug called pexidartinib for the treatment of certain tumors for which surgical removal could cause more harm than good. The main purpose of this study is to gather information about the investigational drug pexidartinib, which may help to treat tumors of pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS). The study consists of two parts with a follow-up period. In Part 1, eligible study participants will be assigned to receive either pexidartinib or matching placebo for 24 weeks. A number of assessments will be carried out during the course of the study, including physical examinations, blood tests, imaging studies, electrocardiograms, and questionnaires. MRI scans will be used to evaluate the response of the tumors to the treatment. Some subjects, assigned to placebo in Part 1 transitioned to pexidartinib for Part 2. Then a protocol amendment was written to allow only pexidartinib patients to continue into Part 2. Part 2 is a long-term treatment phase in which all participants receive open-label pexidartinib. There was also a follow-up period added to Part 2.

Official Title

A Double-blind, Randomized, Placebo-controlled Phase 3 Study of Orally Administered PLX3397 in Subjects With Pigmented Villonodular Synovitis or Giant Cell Tumor of the Tendon Sheath

Stanford Investigator(s)

Kristen N Ganjoo
Kristen N Ganjoo

Professor of Medicine (Oncology)

Raffi S. Avedian, MD
Raffi S. Avedian, MD

Associate Professor of Orthopaedic Surgery


Inclusion Criteria

   1. Age ≥ 18 years.

   2. A diagnosis of PVNS or GCT-TS (i) that has been histologically confirmed either by a
   pathologist at the treating institution or a central pathologist, and (ii) where
   surgical resection would be associated with potentially worsening functional
   limitation or severe morbidity (locally advanced disease), with morbidity determined
   consensually by qualified personnel (eg, two surgeons or a multi-disciplinary tumor

   3. Measurable disease of at least 2 cm and otherwise based on RECIST 1.1, assessed from
   MRI scans by a central radiologist.

   4. Symptomatic disease because of active PVNS or GCT-TS, defined as one or more of the

      1. a worst pain of at least 4 at any time during the week preceding the Screening
      Visit (based on scale of 0 to 10, with 10 representing "pain as bad as you can

      2. a worst stiffness of at least 4 at any time during the week preceding the
      Screening Visit (based on a scale of 0 to 10, with 10 representing "stiffness as
      bad as you can imagine").

   5. Stable prescription of analgesic regimen during the 2 weeks prior to randomization.

   6. During the 2 weeks prior to randomization, at least 4 of 7 consecutive days of Brief
   Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) items and Worst Stiffness
   NRS items completed correctly.

   7. Women of childbearing potential must have a negative serum pregnancy test within the
   14-day period prior to randomization. (Where demanded by local regulations, this test
   may be required within 72 hours of randomization.)

   8. Males and females of childbearing potential are permitted in the study so long as they
   consent to avoid getting their partner pregnant or becoming pregnant, respectively, by
   using a highly effective contraception method, as described below, throughout the
   study and for up to 90 days after completion. Highly effective methods of
   contraception include: intra-uterine device (non-hormonal or hormonal), bilateral
   tubal occlusion, vasectomy, sexual abstinence, or barrier methods (eg, condom,
   diaphragm) used in combination with hormonal methods associated with inhibition of
   ovulation. Women of non-childbearing potential may be included if they are either
   surgically sterile or have been postmenopausal for ≥ 1 year. Women who have
   documentation of at least 12 months of spontaneous amenorrhea and have a follicle
   stimulating hormone (FSH) level > 40 milli-International units (mIU/mL) will be
   considered postmenopausal.

   9. Adequate hematologic, hepatic, and renal function, defined by:

      - Absolute neutrophil count ≥ 1.5 × 10^9/L

      - aspartate aminotransferase/alanine (AST/ALT) ≤ 1.5 × upper limit of normal (ULN)

      - Hemoglobin > 10 g/dL

      - Total bilirubin ≤ 1.5 × ULN

      - Platelet count ≥ 100 × 10^9/L

      - Serum creatinine ≤ 1.5 × ULN

10. Willingness and ability to complete the Worst Pain NRS item, Worst Stiffness NRS item,
   Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function
   Scale, and other self-assessment instruments throughout the study.

11. Willingness and ability to use an electronic diary.

12. Willingness and ability to provide written informed consent prior to any study-related
   procedures and to comply with all study requirements.

Exclusion Criteria

   1. Investigational drug use within 28 days of randomization.

   2. Previous use of pexidartinib or any biologic treatment targeting CSF-1 or the CSF-1R;
   previous use of oral tyrosine kinase inhibitors, eg, imatinib or nilotinib, are

   3. Active cancer (either concurrent or within the last year of starting study treatment)
   that requires therapy (eg, surgical, chemotherapy, or radiation therapy), with the
   exception of adequately treated basal or squamous cell carcinoma of the skin, melanoma
   in-situ, carcinoma in-situ of the cervix or breast, or prostate carcinoma with a
   prostate-specific antigen value <0.2 ng/mL.

   4. Known metastatic PVNS/GCT-TS.

   5. Active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus or known
   active or chronic infection with human immunodeficiency virus.

   6. Known active tuberculosis.

   7. Significant concomitant arthropathy in the affected joint, serious illness,
   uncontrolled infection, or a medical or psychiatric history that, in the
   Investigator's opinion, would likely interfere with the person's study participation
   or the interpretation of his or her results.

   8. Women who are breastfeeding.

   9. A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms

10. MRI contraindications.

11. History of hypersensitivity to any excipients in the investigational product.

12. Inability to swallow capsules.


drug: Pexidartinib

drug: Placebo

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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