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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02371369
First Posted: February 25, 2015
Last Update Posted: October 17, 2017
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.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.
  Purpose

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 Intervention Phase
Pigmented Villonodular Synovitis Giant Cell Tumors of the Tendon Sheath Tenosynovial Giant Cell Tumour Drug: PLX3397 capsule Drug: Placebo capsule matching PLX3397 capsule Phase 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo, Inc.:

Primary Outcome Measures:
  • Percentage of participants achieving complete or partial response [ Time Frame: to 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) at the Week 25 visit based on centrally read MRI scans and RECIST 1.1.


Secondary Outcome Measures:
  • 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

  • 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)

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

Enrollment: 120
Study Start Date: March 2015
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 capsule
Each capsule of PLX3397 will contain 200 mg of PLX3397 HCl
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 capsule matching PLX3397 capsule
Placebo capsule matching PLX3397 capsule

  Eligibility

Information from the National Library of Medicine

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

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


  Show 38 Study Locations
Sponsors and Collaborators
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 Submitted: February 19, 2015
First Posted: February 25, 2015
Last Update Posted: October 17, 2017
Last Verified: October 2017

Keywords provided by Daiichi Sankyo, Inc.:
Pigmented Villonodular Synovitis
Giant Cell Tumors of the Tendon Sheath
Tenosynovial Giant Cell Tumour
PLX3397
Colony Stimulating Factor 1 Receptor (CSF1R) inhibitor

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