We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu
IMPORTANT: Due to the lapse in government funding, the information on this web site may not be up to date, transactions submitted via the web site may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted. Updates regarding government operating status and resumption of normal operations can be found at opm.gov.

PLX3397 Phase 3 Study for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS) (ENLIVEN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02371369
Recruitment Status : Active, not recruiting
First Posted : February 25, 2015
Last Update Posted : November 9, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

This is a Phase 3 clinical study, which aims to evaluate the effectiveness of an investigational drug PLX3397 in the treatment of tumour of pigmented villonodular synovitis or giant cell tumor of the tendon sheath in subjects, for whom surgical removal of the tumour would cause more harm than good. The main purpose of this study is to gather information about the investigational drug PLX3397, which may help to treat these tumours.

The study consists of two parts. In Part 1, eligible study participants will be assigned to receive either PLX3397 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 tumour to the treatment which will be independently assessed by central readers blinded to the treatment assignment. Those subjects, whether assigned to PLX3397 or matching placebo, who have completed Part 1 (i.e, complete 24 weeks of dosing and the Week 25 assessments) will be eligible to advance to Part 2, a long-term treatment phase in which all subjects will receive open-label PLX3397

Condition or disease Intervention/treatment Phase
Pigmented Villonodular Synovitis Giant Cell Tumors of the Tendon Sheath Tenosynovial Giant Cell Tumour Drug: PLX3397 Drug: Placebo Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 2015
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: PLX3397
1000 mg per day for 2 weeks (dose split over morning and evening), then 800 mg per day for 22 weeks (dose split over morning and evening).
Drug: PLX3397
Each capsule of PLX3397 will contain 200 mg of PLX3397 HCl
Other Names:
  • PLX3397 Capsule
  • Pexidartinib
Placebo Comparator: Placebo
1000 mg matching placebo per day for 2 weeks (dose split over morning and evening), then up to 800 mg placebo per day for 22 weeks (dose split over morning and evening).
Drug: Placebo
Placebo capsule matching PLX3397 capsule
Other Name: Placebo Capsule

Outcome Measures

Primary Outcome Measures :
  1. Percentage of participants achieving complete or partial response at Week 25 [ Time Frame: at Week 25 ]
    The percentage of participants who achieved a complete response (CR) or partial response (PR) at the Week 25 visit based on centrally read MRI scans and RECIST 1.1.

  2. Percentage of participants achieving complete or partial response by the end of the trial [ Time Frame: at the end of the trial, assessed up to an estimated total of 36 months ]
    The percentage of participants who achieved a complete response (CR) or partial response (PR) by the end of the trial based on centrally read MRI scans and RECIST 1.1.

Secondary Outcome Measures :
  1. Mean composite score for patient reported outcomes [ Time Frame: to the end of the trial, assessed up to an estimated total of 36 months ]
    Evaluate composite patient-reported outcomes (PROs), including the Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) item, Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale, and Worst Stiffness NRS item, at Week 25

  2. Number of responders based on Tumor Volume Score [ Time Frame: to the end of the trial, assessed up to an estimated total of 36 months ]
    Response based on Tumor Volume Score (TVS)

  3. Mean range of motion [ Time Frame: to the end of the trial, assessed up to an estimated total of 36 months ]
  4. Mean duration of response. [ Time Frame: to the end of the trial, assessed up to an estimated total of 36 months ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age ≥ 18 years.
  • 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 board).
  • Measurable disease of at least 2 cm and otherwise based on RECIST 1.1, assessed from MRI scans by a central radiologist.
  • Symptomatic disease
  • Stable analgesic regimen during the 2 weeks prior to randomization.
  • During the week prior to randomization, at least 4 days of BPI Worst Pain NRS items and Worst Stiffness NRS items completed correctly.
  • Males and females of childbearing potential are permitted in the study as 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: hormonal methods associated with inhibition of ovulation, intra-uterine device; surgical sterilization (including partner's vasectomy) or sexual abstinence. 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 an follicle stimulating hormone (FSH) level >40 milli-international units per milliliter (mIU/mL) will be considered postmenopausal.
  • Adequate hematologic, hepatic, and renal function, defined by:

    • Absolute neutrophil count ≥ 1.5 × 109/L
    • Ratio between the concentrations of the enzymes aspartate transaminase (AST) and alanine transaminase (ALT) in the blood (AST/ALT) ≤ 1.5 × the upper limit of normal (ULN)
    • Hemoglobin > 10 g/dL • Total bilirubin ≤ 1.5 × ULN
    • Platelet count ≥ 100 × 109/L • Serum creatinine ≤ 1.5 × ULN
  • Willingness and ability to complete the BPI Worst Pain NRS item, Worst Stiffness NRS item, PROMIS Physical Function Scale, and other self-assessment instruments throughout the study.
  • Willingness and ability to use an electronic diary.
  • Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.

Exclusion Criteria:

  • Investigational drug use within 28 days of randomization.
  • Previous use of PLX3397 or any biologic treatment targeting Colony Stimulating Factor 1 (CSF1) or the Colony Stimulating Factor 1 Receptor (CSF1R); previous use of oral tyrosine kinase inhibitors, eg, imatinib or nilotinib, are allowed.
  • Active cancer (either concurrent or within the last year of starting study treatment) that requires non-surgical therapy (eg, chemotherapy or radiation therapy), with the exception of PVNS/GCT-TS, surgically treated basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix. Prostate and breast cancer in remission (not receiving active therapy) for > 5 years will be allowed.
  • Known metastatic PVNS/GCT-TS.
  • Active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus or known active or chronic infection with human immunodeficiency virus.
  • Known active tuberculosis.
  • 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.
  • Women who are breastfeeding.
  • A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms (women).
  • MRI contraindications.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02371369

  Hide Study Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259-5499
United States, California
University of Southern California
Los Angeles, California, United States, 90033
Stanford Cancer Center
Palo Alto, California, United States, 94305
UCLA Medical Center
Santa Monica, California, United States, 90404
United States, Florida
Mayo Clinic Cancer Center
Jacksonville, Florida, United States, 32224
Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
: Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New Jersey
MD Anderson Cancer Center at Cooper
Camden, New Jersey, United States, 08103
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke Cancer Center
Durham, North Carolina, United States, 27710
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Australia, New South Wales
Chris O'Brien Lifehouse
Sydney, New South Wales, Australia, 2050
Australia, Queensland
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, Victoria
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
Canada, Quebec
McGill University Health Centre
Montreal, Quebec, Canada, H4A3J1
Herlev Hospital
Herlev, Denmark, 2730
Centre Leon Bérard
Lyon, France, 69373
Institut Gustave Roussy
Villejuif, France, 94800
HELIOS Klinikum Berlin-Buch
Berlin, Germany, 13125
Universitätsklinikum Essen
Essen, Germany, 45147
Military Hospital-State Health Center
Budapest, Hungary, H1134
Istituto Ortopedico Rizzoli
Bologna, BO, Italy, 40136
Istituto Nazionale Tumori-Fondazione IRCCS
Milano, MI, Italy, 20133
Leiden University Medical Center
Leiden, Netherlands, 2333 ZA
Radboud Univ. Medical Center
Nijmegen, Netherlands, 6525 GA
Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie
Warszawa, Poland, 02-781
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital Universitario Virgen del Rocío
Sevilla, Spain, 41013
United Kingdom
University College Hospital
London, United Kingdom, NW12BU
The Royal Marsden NHS Foundation Trust
London, United Kingdom, SW36JJ
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Study Director: Global Team Leader Daiichi Sankyo, Inc.
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02371369     History of Changes
Other Study ID Numbers: PLX108-10
2014-000148-14 ( EudraCT Number )
First Posted: February 25, 2015    Key Record Dates
Last Update Posted: November 9, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at http://www.clinicalstudydatarequest.com. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received EU and US marketing approval on or after 01 January 2014 or by the US or EU Health Authorities when regulatory submissions in both regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States and the European Union from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx

Keywords provided by Daiichi Sankyo, Inc.:
Pigmented Villonodular Synovitis
Giant Cell Tumors of the Tendon Sheath
Tenosynovial Giant Cell Tumour
Colony Stimulating Factor 1 Receptor (CSF1R) inhibitor

Additional relevant MeSH terms:
Giant Cell Tumors
Giant Cell Tumor of Tendon Sheath
Synovitis, Pigmented Villonodular
Joint Diseases
Musculoskeletal Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Muscular Diseases