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History of Changes for Study: NCT02371369
PLX3397 Phase 3 Study for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS)
Latest version (submitted April 11, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 February 19, 2015 None (earliest Version on record)
2 March 25, 2015 Recruitment Status, Study Status, Contacts/Locations, Eligibility, Oversight and Study Identification
3 July 28, 2015 Contacts/Locations and Study Status
4 October 19, 2015 Contacts/Locations and Study Status
5 January 18, 2016 Contacts/Locations and Study Status
6 February 17, 2016 Study Status and Contacts/Locations
7 August 22, 2016 Study Status
8 September 27, 2016 Recruitment Status, Contacts/Locations and Study Status
9 October 14, 2016 Recruitment Status and Study Status
10 October 17, 2016 Recruitment Status, Outcome Measures, Study Status, Study Design, Eligibility and Conditions
11 October 20, 2016 Study Design and Study Status
12 April 13, 2017 Study Status, Outcome Measures and Study Design
13 July 5, 2017 Study Status and Contacts/Locations
14 August 30, 2017 Study Status
15 September 28, 2017 Study Status
16 September 29, 2017 Study Status and Study Identification
17 October 13, 2017 Study Status
18 November 7, 2017 Study Status, Outcome Measures, Arms and Interventions, IPDSharing and Contacts/Locations
19 March 13, 2018 Arms and Interventions, Outcome Measures, Study Status, Contacts/Locations, Study Design, Conditions, Eligibility, Study Description and Study Identification
20 June 22, 2018 Study Status
21 July 30, 2018 Study Status
22 January 20, 2019 IPDSharing, Study Status, Eligibility, Arms and Interventions and Study Description
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Results Submission Events
23 January 6, 2020 Study Status, Outcome Measures, Study Design, Document Section, Results, IPDSharing and Eligibility
24 January 11, 2021 Study Status
25 June 1, 2021 Recruitment Status and Study Status
26 April 11, 2022 Adverse Events, Outcome Measures, Participant Flow, Document Section, Study Status, More Information and Eligibility
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Study NCT02371369
Submitted Date:  February 19, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: PLX108-10
Brief Title: PLX3397 Phase 3 Study for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS)
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
Secondary IDs:
Open or close this module Study Status
Record Verification: February 2015
Overall Status: Not yet recruiting
Study Start: March 2015
Primary Completion: March 2018 [Anticipated]
Study Completion: March 2018 [Anticipated]
First Submitted: February 19, 2015
First Submitted that
Met QC Criteria:
February 19, 2015
First Posted: February 25, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
February 19, 2015
Last Update Posted: February 25, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Daiichi Sankyo, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module 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

Detailed Description:
Open or close this module Conditions
Conditions: Pigmented Villonodular Synovitis
Giant Cell Tumors of the Tendon Sheath
Tenosynovial Giant Cell Tumour
Keywords: Pigmented Villonodular Synovitis
Giant Cell Tumors of the Tendon Sheath
Tenosynovial Giant Cell Tumour
PLX3397
CSF1R inhibitor
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 126 [Anticipated]
Open or close this module Arms and Interventions
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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. percentage of subjects achieving complete or partial response
[ Time Frame: week 25 ]

The proportion of subjects who achieve 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:
1. composite of patient reported outcomes
[ Time Frame: week 25 ]

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. response based on Tumor Volume Score
[ Time Frame: week 25 ]

response based on Tumor Volume Score (TVS)
3. range of motion
[ Time Frame: week 25 ]

4. duration of response.
[ Time Frame: week 25 ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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 because of active PVNS or GCT-TS, defined as one or more of the following: a. a worst pain of at least 4 at any time during the preceding week (based on scale of 0 to 10, with 10 representing "pain as bad as you can imagine"). b. a worst stiffness of at least 4 at any time during the preceding week (based on a scale of 0 to 10, with 10 representing "stiffness as bad as you can imagine").
  • 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 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: 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 FSH level >40 mIU/mL will be considered postmenopausal.
  • Male and female subjects of childbearing potential must agree to use two of the following during the study and for 90 days after the last dose of study treatment: (i) an oral, injected, or implanted hormonal method of contraception; (ii) placement of an intrauterine device or intrauterine system; (iii) a barrier method of contraception (condom or occlusive cap) in conjunction with a spermicide. Alternatively, this requirement could be fulfilled by completely abstaining from intercourse during the above-mentioned time period or, for male subjects or partners, agreeing to undergo sterilization. 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 FSH level >40 mIU/mL will be considered postmenopausal.
  • Adequate hematologic, hepatic, and renal function, defined by:
    • Absolute neutrophil count ≥ 1.5 × 109/L • AST/ALT ≤ 1.5 × 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 a 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 CSF-1 or the 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.
Open or close this module Contacts/Locations
Central Contact Person: Lori Dismant
Telephone: 1-623-322-4301
Email: ldismant@novellaclinical.com
Locations: United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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