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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02371369
Ethics application status
Date submitted
19/02/2015
Date registered
25/02/2015
Date last updated
10/01/2020

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 - Complete response (CR) and partial responses (PR) were assessed based on centrally-read magnetic resonance imaging (MRI) scans and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). A CR was defined as disappearance of all tumors and a PR was defined as at least a 30% decrease in the sum of diameters of target tumors using the baseline sum diameters as the reference.
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 - Range of motion (ROM) of the joint was assessed by a qualified, independent, and blinded or third-party assessors at the clinical site. Measurements were recorded in degrees. At baseline, the plane of movement with the smallest relative value (worst) was identified and this plane was used for evaluating the relative change of motion subsequently. Only the plane with the worst impaired ROM at baseline was selected for subsequent analyses.
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 - Complete response (CR) and partial response (PR) were assessed using tumor volume score (TVS). A CR was defined as disappearance of all tumors and a PR was defined as at least a 30% decrease in the sum of diameters of target tumors using the baseline sum diameters as the reference. TVS is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor.
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 - The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess physical function of the upper and lower limbs. The scale ranged from 1 defined as 'unable to do' or 'cannot do' to 5 defined as 'without any difficulty' or 'not at all', where higher scores represent better outcomes.
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 - The Worst Stiffness Numeric Rating Scale (NRS) was a 1-item, self-administered questionnaire assessing the "worst" stiffness in the last 24 hours. The NRS for this item ranged from 0 (no stiffness) to 10 (stiffness as bad as you can imagine).
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 - The Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale Score (NRS) was a 1-item, self-administered questionnaire assessing the "worst" pain in the last 24 hours. The NRS for this item ranged from 0 (no pain) to 10 (pain as bad as you can imagine).
Timepoint [5] 0 0
Week 25
Secondary outcome [6] 0 0
Number of Responders to Pexidartinib With and Without Disease Progression by Week 96 - Duration of response (DOR) based on RECIST 1.1 is defined as the date of the first recorded response to the first date of documented disease progression. The overall number of responses and the number of participants with and without disease progression was assessed.
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 by Week 120 - Tumor Volume Score (TVS) is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor. The overall number of responses and the number of participants with and without disease progression was assessed.
Timepoint [7] 0 0
By Week 120
Secondary outcome [8] 0 0
Percentage of Participants Reporting Frequent (=10%) Treatment-Emergent Adverse Events by Preferred Term - Treatment-emergent adverse events (TEAEs) were defined as adverse events that started or worsened after the first dose of treatment and within 28 days after the last dose. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 was used to grade adverse events. Any Grade and Grade =3 (severe) TEAEs are reported. TEAEs were coded using MedDRA version 17.1.
Timepoint [8] 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 × 109/L

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

- Hemoglobin > 10 g/dL

- Total bilirubin = 1.5 × ULN

- Platelet count = 100 × 109/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
Gender
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02371369
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Team Leader
Address 0 0
Daiichi Sankyo, Inc.
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

Summary results
Other publications