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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02371369




Registration number
NCT02371369
Ethics application status
Date submitted
19/02/2015
Date registered
25/02/2015

Titles & IDs
Public title
Phase 3 Study of Pexidartinib for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS)
Scientific 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 ID [1] 0 0
2014-000148-14
Secondary ID [2] 0 0
PLX108-10
Universal Trial Number (UTN)
Trial acronym
ENLIVEN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pigmented Villonodular Synovitis 0 0
Giant Cell Tumors of the Tendon Sheath 0 0
Tenosynovial Giant Cell Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Other cancer types
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pexidartinib
Treatment: Drugs - Placebo

Experimental: Part 1 - Pexidartinib - Participants received blinded treatment of pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks

Placebo comparator: Part 1 - Placebo - Participants received blinded treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks

Experimental: Part 2 - All Pexidartinib - Participants received pexidartinib in Part 1 and in Part 2 at their prescribed dose

Experimental: Part 2 - Placebo-Pexidartinib - Participants received placebo in Part 1 and pexidartinib in Part 2 at their prescribed dose


Treatment: Drugs: Pexidartinib
Each capsule contains 200 mg of pexidartinib for oral administration

Treatment: Drugs: Placebo
Placebo capsule matching pexidartinib capsule for oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Symptomatic, Locally Advanced Tenosynovial Giant Cell Tumor (TGCT) Achieving Complete or Partial Response to Pexidartinib Compared With That of Placebo Per Response Evaluation Criteria in Solid Tumors Version 1.1 at Week 25
Timepoint [1] 0 0
Week 25
Secondary outcome [1] 0 0
Mean Change From Baseline For Range of Motion (ROM) Score in Participants Receiving Pexidartinib Compared With Those on Placebo Up to Week 25
Timepoint [1] 0 0
Baseline, Week 13, and Week 25
Secondary outcome [2] 0 0
Percentage of Participants With Symptomatic, Locally Advanced Tenosynovial Giant Cell Tumor (TGCT) Achieving Complete or Partial Response Based on Tumor Volume Score (TVS) After Receiving Pexidartinib Compared With Those on Placebo at Week 25
Timepoint [2] 0 0
Week 25
Secondary outcome [3] 0 0
Mean Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score in Participants Receiving Pexidartinib Compared With Those on Placebo Up to Week 25
Timepoint [3] 0 0
at Week 9 , Week 17, and Week 25
Secondary outcome [4] 0 0
Mean Change From Baseline for Worst Stiffness Numeric Rating Scale Score (NRS) in Participants Receiving Pexidartinib Compared With Those on Placebo Up to Week 25
Timepoint [4] 0 0
Baseline, Week 9, Week 17, and Week 25
Secondary outcome [5] 0 0
Percentage of Participants Who Responded With a Decrease of at Least 30% in the Mean Brief Pain Inventory Worst Pain Numeric Rating Scale Score Among Participants Receiving Pexidartinib Compared With Those on Placebo at Week 25
Timepoint [5] 0 0
Week 25
Secondary outcome [6] 0 0
Number of Responders to Pexidartinib With and Without Disease Progression
Timepoint [6] 0 0
By Week 96
Secondary outcome [7] 0 0
Number of Responders to Pexidartinib With and Without Disease Progression Based on Tumor Volume Score
Timepoint [7] 0 0
By Week 120
Secondary outcome [8] 0 0
Duration of Response (DOR) Based on RECIST 1.1
Timepoint [8] 0 0
Date of first documentation of objective response up to date of first documentation of progressive disease, assessed up to end of study (approximately 71 months)
Secondary outcome [9] 0 0
Duration of Response (DOR) Based on Tumor Volume Score (TVS)
Timepoint [9] 0 0
Date of first documentation of objective response up to date of first documentation of progressive disease, assessed up to end of study (approximately 71 months)
Secondary outcome [10] 0 0
Percentage of Participants Reporting Frequent (=10%) Treatment-Emergent Adverse Events by Preferred Term
Timepoint [10] 0 0
After the first dose of treatment up to 28 days after the last dose

Eligibility
Key inclusion criteria
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 board).
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 following:

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 imagine").
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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 allowed.
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 (women).
10. MRI contraindications.
11. History of hypersensitivity to any excipients in the investigational product.
12. Inability to swallow capsules.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/05/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/04/2021
Sample size
Target
Accrual to date
Final
120
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Sydney
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Sydney
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3000 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Denmark
State/province [17] 0 0
Herlev
Country [18] 0 0
France
State/province [18] 0 0
Lyon
Country [19] 0 0
France
State/province [19] 0 0
Villejuif
Country [20] 0 0
Germany
State/province [20] 0 0
Berlin
Country [21] 0 0
Germany
State/province [21] 0 0
Essen
Country [22] 0 0
Hungary
State/province [22] 0 0
Budapest
Country [23] 0 0
Italy
State/province [23] 0 0
BO
Country [24] 0 0
Italy
State/province [24] 0 0
MI
Country [25] 0 0
Netherlands
State/province [25] 0 0
Leiden
Country [26] 0 0
Netherlands
State/province [26] 0 0
Nijmegen
Country [27] 0 0
Poland
State/province [27] 0 0
Warszawa
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Sevilla
Country [30] 0 0
United Kingdom
State/province [30] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Daiichi Sankyo
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Team Leader
Address 0 0
Daiichi Sankyo
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. 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://vivli.org/ourmember/daiichi-sankyo/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Available to whom?
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, the European Union and/or Japan 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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/daiichi-sankyo/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02371369