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

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02371369
• Collaborator: (none)
• Enrollment: 120
• Locations: 39
• Arms: 4
• Actual Duration (Months): 71.7
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pigmented Villonodular Synovitis; Giant Cell Tumors of the Tendon Sheath; Tenosynovial Giant Cell Tumor	Drug: Pexidartinib; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) in Part 1, Open-label (no masking) in Part 2
• 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: May 11, 2015
• Actual Primary Completion Date: Mar 27, 2017
• Actual Study Completion Date: Apr 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
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	Drug: Pexidartinib; Each capsule contains 200 mg of pexidartinib for oral administration; Other Names: PLX3397 Pexidartinib hydrochloride (HCl)
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	Drug: Placebo; Placebo capsule matching pexidartinib capsule for oral administration; Other Names: Placebo Capsule
Experimental: Part 2 - All Pexidartinib Participants received pexidartinib in Part 1 and in Part 2 at their prescribed dose	Drug: Pexidartinib; Each capsule contains 200 mg of pexidartinib for oral administration; Other Names: PLX3397 Pexidartinib hydrochloride (HCl)
Experimental: Part 2 - Placebo-Pexidartinib Participants received placebo in Part 1 and pexidartinib in Part 2 at their prescribed dose	Drug: Pexidartinib; Each capsule contains 200 mg of pexidartinib for oral administration; Other Names: PLX3397 Pexidartinib hydrochloride (HCl) ; Drug: Placebo; Placebo capsule matching pexidartinib capsule for oral administration; Other Names: Placebo Capsule

Outcome Measures

Primary Outcome Measures

1. 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 [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.

Secondary Outcome Measures

1. Mean Change From Baseline For Range of Motion (ROM) Score in Participants Receiving Pexidartinib Compared With Those on Placebo Up to Week 25 [Baseline, Week 13, and 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.

2. 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 [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.

3. 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 [at Week 9 , Week 17, and 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.

4. 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 [Baseline, Week 9, Week 17, and 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).

5. 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 [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).

6. 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.

7. 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.

8. Duration of Response (DOR) Based on RECIST 1.1 [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)]

   Duration of response (DOR) based on RECIST 1.1 is defined from the date of the first recorded evidence of response to the first date of documented disease progression.

9. Duration of Response (DOR) Based on Tumor Volume Score (TVS) [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)]

   Duration of response (DOR) based on TVS is defined from the date of the first recorded evidence of response to the first date of documented disease progression.

10. Percentage of Participants Reporting Frequent (≥10%) Treatment-Emergent Adverse Events by Preferred Term [After the first dose of treatment up to 28 days after the last dose]

    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.

Other Outcome Measures

1. 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 by Week 49 [By Week 49]

   Complete (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.

2. Mean Change From Baseline For Range of Motion (ROM) Score in Participants Receiving Pexidartinib Compared With Those on Placebo by Week 49 [By Week 49]

   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.

3. 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 by Week 49 [By Week 49]

   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.

4. Mean Change From Baseline for Worst Stiffness Numeric Rating Scale Score (NRS) in Participants Receiving Pexidartinib Compared With Those on Placebo by Week 49 [Baseline, Week 25, and Week 49]

   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).

5. Mean Change From Baseline for Worst Pain Numeric Rating Scale Score (NRS) in Participants Receiving Pexidartinib Compared With Those on Placebo by Week 49 [By Week 49]

   The Brief Pain Inventory (BPI) Worst Pain 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).

6. 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 by Week 49 [By Week 49]

   Best overall response (CR or PR) was assessed using tumor volume score (TVS) in the ITT population. Tumor Volume Score 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

5. 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").

6. 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").

7. Stable prescription of analgesic regimen during the 2 weeks prior to randomization.

8. 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.

9. 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.)

10. 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.

11. 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

1. 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.

2. Willingness and ability to use an electronic diary.

3. Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259-5499
2	University of Southern California	Los Angeles	California	United States	90033
3	Stanford Cancer Center	Palo Alto	California	United States	94305
4	UCLA Medical Center	Santa Monica	California	United States	90404
5	Mayo Clinic Cancer Center	Jacksonville	Florida	United States	32224
6	Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
7	Moffitt Cancer Center	Tampa	Florida	United States	33612
8	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
9	: Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
10	Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
11	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
12	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
13	MD Anderson Cancer Center at Cooper	Camden	New Jersey	United States	08103
14	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
15	Duke Cancer Center	Durham	North Carolina	United States	27710
16	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239
17	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
18	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
19	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
20	Chris O'Brien Lifehouse	Sydney	New South Wales	Australia	2050
21	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
22	Peter MacCallum Cancer Centre	East Melbourne	Victoria	Australia	3000
23	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G2M9
24	McGill University Health Centre	Montreal	Quebec	Canada	H4A3J1
25	Herlev Hospital	Herlev		Denmark	2730
26	Centre Leon Bérard	Lyon		France	69373
27	Institut Gustave Roussy	Villejuif		France	94800
28	HELIOS Klinikum Berlin-Buch	Berlin		Germany	13125
29	Universitätsklinikum Essen	Essen		Germany	45147
30	Military Hospital-State Health Center	Budapest		Hungary	H1134
31	Istituto Ortopedico Rizzoli	Bologna	BO	Italy	40136
32	Istituto Nazionale Tumori-Fondazione IRCCS	Milano	MI	Italy	20133
33	Leiden University Medical Center	Leiden		Netherlands	2333 ZA
34	Radboud Univ. Medical Center	Nijmegen		Netherlands	6525 GA
35	Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie	Warszawa		Poland	02-781
36	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
37	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
38	University College Hospital	London		United Kingdom	NW12BU
39	The Royal Marsden NHS Foundation Trust	London		United Kingdom	SW36JJ

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

• Study Director: Global Team Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 22, 2020

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT02371369
• Other Study ID Numbers: PLX108-10; 2014-000148-14
• First Posted: Feb 25, 2015
• Last Update Posted: May 11, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Daiichi Sankyo, Inc.: PLX3397; Pexidartinib; Colony Stimulating Factor 1 Receptor (CSF-1R) inhibitor
• Additional relevant MeSH terms: Neoplasms; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Synovitis, Pigmented Villonodular; Synovitis

Study Results

Participant Flow

Recruitment Details	Part 1 was a double-blind, randomized, Pexidartinib or placebo in participants with symptomatic TGCT for whom surgical resection would be associated with potentially worsening functional limitation or severe morbidity. Part 2 is a long-term treatment phase in which all eligible participants received open-label Pexidartinib.
Pre-assignment Detail	Participants were screened for inclusion and exclusion criteria. Screening procedures were performed after consent was obtained and within the 42 days before the first dose of study drug, unless otherwise noted.

Arm/Group Title	Pexidartinib Part 1, Then Pexidartinib Part 2	Placebo Part 1, Then Pexidartinib Part 2
Arm/Group Description	Participants received Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks in Part 1 of study. Eligible participants from this group also received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 of study. Eligible participants from this group also received Pexidartinib in Part 2 at their prescribed dose. Placebo: Placebo capsule matching Pexidartinib capsule for oral administration. Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration (Part 2).
Period Title: Part 1
STARTED	61	59
COMPLETED	52	48
NOT COMPLETED	9	11
Period Title: Part 1
STARTED	48	30
COMPLETED	0	0
NOT COMPLETED	48	30

Baseline Characteristics

Arm/Group Title	Pexidartinib Part 1, Then Pexidartinib Part 2	Placebo Part 1, Then Pexidartinib Part 2	Total
Arm/Group Description	Participants received Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks in Part 1 of study. Eligible participants from this group also received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 of study. Eligible participants from this group also received Pexidartinib in Part 2 at their prescribed dose. Placebo: Placebo capsule matching pexidartinib capsule for oral administration. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration (Part 2).	Total of all reporting groups
Overall Participants	61	59	120
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	57 93.4%	56 94.9%	113 94.2%
>=65 years	4 6.6%	3 5.1%	7 5.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.6 (13.2)	44.3 (13.6)	44.5 (13.4)
Sex: Female, Male (Count of Participants)
Female	35 57.4%	36 61%	71 59.2%
Male	26 42.6%	23 39%	49 40.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 3.3%	0 0%	2 1.7%
Asian	1 1.6%	2 3.4%	3 2.5%
Native Hawaiian or Other Pacific Islander	2 3.3%	2 3.4%	4 3.3%
Black or African American	3 4.9%	1 1.7%	4 3.3%
White	52 85.2%	54 91.5%	106 88.3%
More than one race	1 1.6%	0 0%	1 0.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	2 3.3%	3 5.1%	5 4.2%
Netherlands	7 11.5%	4 6.8%	11 9.2%
Hungary	2 3.3%	1 1.7%	3 2.5%
United States	23 37.7%	22 37.3%	45 37.5%
Denmark	1 1.6%	2 3.4%	3 2.5%
Poland	2 3.3%	0 0%	2 1.7%
Italy	8 13.1%	9 15.3%	17 14.2%
United Kingdom	0 0%	1 1.7%	1 0.8%
Australia	5 8.2%	7 11.9%	12 10%
France	2 3.3%	5 8.5%	7 5.8%
Germany	4 6.6%	2 3.4%	6 5%
Spain	5 8.2%	3 5.1%	8 6.7%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	Week 25

Outcome Measure Data

Analysis Population Description

Best overall response was assessed in the Intent-to-Treat (ITT) population.

Arm/Group Title	Pexidartinib Part 1	Placebo Part 1
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Measure Participants	61	59
Complete Response (CR)	14.8 24.3%	0 0%
Partial Response (PR)	24.6 40.3%	0 0%
Response (CR or PR)	39.3 64.4%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pexidartinib Part 1, Placebo Part 1
	Comments	Treatment comparison between the pexidartinib and placebo groups at Week 25
	Type of Statistical Test	Other
	Comments	Treatment comparison analysis
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher's Exact Test
	Comments

2. Secondary Outcome

Title	Mean Change From Baseline For Range of Motion (ROM) Score in Participants Receiving Pexidartinib Compared With Those on Placebo Up to Week 25
Description	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.
Time Frame	Baseline, Week 13, and Week 25

Outcome Measure Data

Analysis Population Description

Range of motion was assessed in the ITT population in participants where data were available.

Arm/Group Title	Pexidartinib Part 1	Placebo Part 1
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Measure Participants	61	59
Baseline	62.5 (3.2)	62.9 (2.9)
Week 13	13.0 (2.3)	4.8 (2.6)
Week 25	15.1 (2.1)	6.2 (2.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pexidartinib Part 1, Placebo Part 1
	Comments	Treatment comparison between the pexidartinib and placebo groups at Week 25
	Type of Statistical Test	Other
	Comments	Treatment comparison analysis
Statistical Test of Hypothesis	p-Value	0.0043
	Comments
	Method	Fisher's Exact Test
	Comments

3. Secondary Outcome

Title	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
Description	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.
Time Frame	Week 25

Outcome Measure Data

Analysis Population Description

Best overall response was assessed in the ITT population.

Arm/Group Title	Pexidartinib Part 1	Placebo Part 1
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Measure Participants	61	59
Complete Response (CR)	4.9 8%	0 0%
Partial Response (PR)	50.8 83.3%	0 0%
Response (CR or PR)	55.7 91.3%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pexidartinib Part 1, Placebo Part 1
	Comments	Treatment comparison between the pexidartinib and placebo groups at Week 25
	Type of Statistical Test	Other
	Comments	Treatment comparison analysis
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher's Exact Test
	Comments

4. Secondary Outcome

Title	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
Description	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.
Time Frame	at Week 9 , Week 17, and Week 25

Outcome Measure Data

Analysis Population Description

Physical function was assessed in the ITT population in participants where data were available.

Arm/Group Title	Pexidartinib Part 1	Placebo Part 1
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Measure Participants	61	59
Week 9	2.8 (1.0)	-0.4 (0.8)
Week 17	3.2 (1.1)	0.2 (1.0)
Week 25	4.1 (1.1)	-0.9 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pexidartinib Part 1, Placebo Part 1
	Comments	Treatment comparison between pexidartinib and placebo groups at Week 25
	Type of Statistical Test	Other
	Comments	Treatment comparison analysis
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	Mixed effects model for repeated measure
	Comments

5. Secondary Outcome

Title	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
Description	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).
Time Frame	Baseline, Week 9, Week 17, and Week 25

Outcome Measure Data

Analysis Population Description

Worst stiffness was assessed in the ITT population.

Arm/Group Title	Pexidartinib Part 1	Placebo Part 1
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Measure Participants	61	59
Baseline	5.6 (0.2)	5.9 (0.3)
Week 9	-1.5 (0.3)	-0.5 (0.3)
Week 17	-2.4 (0.3)	-0.4 (0.3)
Week 25	-2.5 (0.3)	-0.3 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pexidartinib Part 1, Placebo Part 1
	Comments	Treatment comparison between the pexidartinib and placebo groups at Week 25
	Type of Statistical Test	Other
	Comments	Treatment comparison analysis
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed effects model for repeated measure
	Comments

6. Secondary Outcome

Title	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
Description	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).
Time Frame	Week 25

Outcome Measure Data

Analysis Population Description

Worst pain was assessed in the ITT population.

Arm/Group Title	Pexidartinib Part 1	Placebo Part 1
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.
Measure Participants	61	59
Number [percentage of participants]	31.1 51%	15.3 25.9%

7. Secondary Outcome

Title	Number of Responders to Pexidartinib With and Without Disease Progression
Description	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.
Time Frame	By Week 96

Outcome Measure Data

Analysis Population Description

The overall number of responses and the number of participants with and without disease progression were assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Pexidartinib Part 2 only, All Pexidartinib Treated participants, . Participants randomized to Placebo Part 1 only were not analyzed.

Arm/Group Title	Pexidartinib Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2	All Pexidartinib Treated
Arm/Group Description	Part 1: Participants received treatment of pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Part 2: Participants also received pexidartinib at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration	Participants that received placebo in part 1 and received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration	All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Measure Participants	61	30	91
Number of responses	23 37.7%	12 20.3%	35 29.2%
Week 12 (Day 84); Without disease progression	23 37.7%	12 20.3%	35 29.2%
Week 12 (Day 84); With disease progression	0 0%	0 0%	0 0%
Week 24 (Day 168); Without disease progression	23 37.7%	12 20.3%	35 29.2%
Week 24 (Day 168); With disease progression	0 0%	0 0%	0 0%
Week 48 (Day 336); Without disease progression	15 24.6%	9 15.3%	24 20%
Week 48 (Day 336); With disease progression	1 1.6%	0 0%	1 0.8%
Week 72 (Day 504); Without disease progression	9 14.8%	3 5.1%	12 10%
Week 72 (Day 504); With disease progression	1 1.6%	0 0%	1 0.8%
Week 96 (Day 672); Without disease progression	2 3.3%	1 1.7%	3 2.5%
Week 96 (Day 672); With disease progression	1 1.6%	0 0%	1 0.8%

8. Secondary Outcome

Title	Number of Responders to Pexidartinib With and Without Disease Progression Based on Tumor Volume Score
Description	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.
Time Frame	By Week 120

Outcome Measure Data

Analysis Population Description

The overall number of responses and the number of participants with and without disease progression was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Pexidartinib Part 2 only; and All Pexidartinib Treated participants. Participants who received Placebo Part 1 only were not analyzed.

Arm/Group Title	Pexidartinib in Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2	All Pexidartinib Treated
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose. Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	All participants who received pexidartinib in Part 1 and Part 2 as well as those who received pexidartinib in Part 2 only.
Measure Participants	61	30	91
Number of responders	34 55.7%	18 30.5%	52 43.3%
Week 12 (Day 84); Without disease progression	33 54.1%	18 30.5%	51 42.5%
Week 12 (Day 84); With disease progression	0 0%	0 0%	0 0%
Week 24 (Day 168); Without disease progression	32 52.5%	18 30.5%	50 41.7%
Week 24 (Day 168); With disease progression	0 0%	0 0%	0 0%
Week 48 (Day 336); Without disease progression	22 36.1%	13 22%	35 29.2%
Week 48 (Day 336); With disease progression	3 4.9%	1 1.7%	4 3.3%
Week 72 (Day 504); Without disease progression	13 21.3%	3 5.1%	16 13.3%
Week 72 (Day 504); With disease progression	3 4.9%	1 1.7%	4 3.3%
Week 96 (Day 672); Without disease progression	3 4.9%	1 1.7%	4 3.3%
Week 96 (Day 672); With disease progression	3 4.9%	1 1.7%	4 3.3%
Week 120 (Day 840); Without disease progression	1 1.6%	0 0%	1 0.8%
Week 120 (Day 840); With disease progression	3 4.9%	1 1.7%	4 3.3%

9. Secondary Outcome

Title	Duration of Response (DOR) Based on RECIST 1.1
Description	Duration of response (DOR) based on RECIST 1.1 is defined from the date of the first recorded evidence of response to the first date of documented disease progression.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

DOR was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Pexidartinib Part 2 only. Participants randomized to Placebo Part 1 only were not analyzed. DOR was based on numbers of responders only.

Arm/Group Title	Pexidartinib Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2
Arm/Group Description	Part 1: Participants received treatment of pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Part 2: Participants also received pexidartinib at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration	Participants that received placebo in part 1 and received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration
Measure Participants	37	18
Median (95% Confidence Interval) [months]	NA	NA

10. Secondary Outcome

Title	Duration of Response (DOR) Based on Tumor Volume Score (TVS)
Description	Duration of response (DOR) based on TVS is defined from the date of the first recorded evidence of response to the first date of documented disease progression.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

DOR was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Pexidartinib Part 2 only. Participants randomized to Placebo Part 1 only were not analyzed. DOR was based on numbers of responders only.

Arm/Group Title	Pexidartinib Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2
Arm/Group Description	Part 1: Participants received treatment of pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Part 2: Participants also received pexidartinib at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration	Participants that received placebo in part 1 and received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration
Measure Participants	41	21
Median (95% Confidence Interval) [months]	52.70	NA

11. Secondary Outcome

Title	Percentage of Participants Reporting Frequent (≥10%) Treatment-Emergent Adverse Events by Preferred Term
Description	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.
Time Frame	After the first dose of treatment up to 28 days after the last dose

Outcome Measure Data

Analysis Population Description

All safety events were assessed in the Safety Analysis Set.

Arm/Group Title	Pexidartinib Part 1	Placebo Part 1	Pexidartinib Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2	All Pexidartinib Treated
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day ) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching Pexidartinib capsule for oral administration.	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose. Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Measure Participants	61	59	61	30	91
Any Hair color changes	67.2 110.2%	3.4 5.8%	73.8 61.5%	83.3 NaN	76.9 NaN
Grade ≥3 Hair color changes	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Pruritis	9.8 16.1%	3.4 5.8%	16.4 13.7%	20.0 NaN	17.6 NaN
Grade ≥3 Pruritis	0 0%	0 0%	1.6 1.3%	0 NaN	1.1 NaN
Any Rash maculopapular	9.8 16.1%	1.7 2.9%	14.8 12.3%	10.0 NaN	13.2 NaN
Grade ≥3 Rash maculopapular	0 0%	0 0%	1.6 1.3%	0 NaN	1.1 NaN
Any Pruritis generalized	8.2 13.4%	0 0%	8.2 6.8%	10.0 NaN	8.8 NaN
Grade ≥3 Pruritis generalized	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Erythema	1.6 2.6%	0 0%	3.3 2.8%	20.0 NaN	8.8 NaN
Grade ≥3 Erythema	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Dry skin	3.3 5.4%	3.4 5.8%	6.6 5.5%	10.0 NaN	7.7 NaN
Grade ≥3 Dry skin	0 0%	0 0%	0 0%	3.3 NaN	1.1 NaN
Any Photosensitivity reaction	0 0%	0 0%	1.6 1.3%	10.0 NaN	4.4 NaN
Grade ≥3 Photosensitivity reaction	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Nausea	37.7 61.8%	40.7 69%	44.3 36.9%	20.0 NaN	36.3 NaN
Grade ≥3 Nausea	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Diarrhea	19.7 32.3%	25.4 43.1%	26.2 21.8%	30.0 NaN	27.5 NaN
Grade ≥3 Diarrhea	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Vomiting	19.7 32.3%	5.1 8.6%	23.0 19.2%	6.7 NaN	17.6 NaN
Grade ≥3 Vomiting	1.6 2.6%	0 0%	1.6 1.3%	0 NaN	1.1 NaN
Any Abdominal Pain	16.4 26.9%	10.2 17.3%	21.3 17.8%	6.7 NaN	16.5 NaN
Grade ≥3 Abdominal Pain	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Dry mouth	9.8 16.1%	3.4 5.8%	13.1 10.9%	13.3 NaN	13.2 NaN
Grade ≥3 Dry mouth	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Constipation	11.5 18.9%	5.1 8.6%	14.8 12.3%	10.0 NaN	13.2 NaN
Grade ≥3 Constipation	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Stomatitis	6.6 10.8%	1.7 2.9%	8.2 6.8%	10.0 NaN	8.8 NaN
Grade ≥3 Stomatitis	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Fatigue	54.1 88.7%	35.6 60.3%	55.7 46.4%	26.7 NaN	46.2 NaN
Grade ≥3 Fatigue	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Edema peripheral	13.1 21.5%	3.4 5.8%	16.4 13.7%	20.0 NaN	17.6 NaN
Grade ≥3 Edema peripheral	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Face edema	13.1 21.5%	1.7 2.9%	14.8 12.3%	20.0 NaN	16.5 NaN
Grade ≥3 Face edema	0 0%	0 0%	1.6 1.3%	3.3 NaN	2.2 NaN
Any Asthenia	9.8 16.1%	5.1 8.6%	11.5 9.6%	20.0 NaN	14.3 NaN
Grade ≥3 Asthenia	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Pyrexia	6.6 10.8%	1.7 2.9%	8.2 6.8%	13.3 NaN	9.9 NaN
Grade ≥ Pyrexia	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any AST increased	39.3 64.4%	0 0%	44.3 36.9%	16.7 NaN	35.2 NaN
Grade ≥3 AST increased	9.8 16.1%	0 0%	9.8 8.2%	6.7 NaN	8.8 NaN
Any ALT increased	27.9 45.7%	1.7 2.9%	31.1 25.9%	23.3 NaN	28.6 NaN
Grade ≥3 ALT increased	9.8 16.1%	0 0%	9.8 8.2%	10.0 NaN	9.9 NaN
Any ALP increased	14.8 24.3%	0 0%	14.8 12.3%	3.3 NaN	11.0 NaN
Grade ≥3 ALP increased	6.6 10.8%	0 0%	6.6 5.5%	3.3 NaN	5.5 NaN
Any LDH increased	11.5 18.9%	0 0%	11.5 9.6%	10.0 NaN	11.0 NaN
Grade ≥3 LDH increased	1.6 2.6%	0 0%	1.6 1.3%	0 NaN	1.1 NaN
Any Weight increased	3.3 5.4%	0 0%	4.9 4.1%	10.0 NaN	6.6 NaN
Grade ≥3 Weight increased	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Dysgeusia	24.6 40.3%	1.7 2.9%	27.9 23.3%	23.3 NaN	26.4 NaN
Grade ≥3 Dysgeusia	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Headache	19.7 32.3%	18.6 31.5%	23.0 19.2%	20.0 NaN	22.0 NaN
Grade ≥3 Headache	0 0%	0 0%	1.6 1.3%	0 NaN	1.1 NaN
Any Dizziness	9.8 16.1%	15.3 25.9%	13.1 10.9%	13.3 NaN	13.2 NaN
Grade ≥3 Dizziness	1.6 2.6%	0 0%	1.6 1.3%	0 NaN	1.1 NaN
Any Paresthesia	1.6 2.6%	1.7 2.9%	8.2 6.8%	10.0 NaN	8.8 NaN
Grade ≥3 Paresthesia	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Memory impairment	0 0%	1.7 2.9%	1.6 1.3%	10.0 NaN	4.4 NaN
Grade ≥3 Memory impairment	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Arthralgia	23.0 37.7%	25.4 43.1%	27.9 23.3%	30.0 NaN	28.6 NaN
Grade ≥3 Arthralgia	3.3 5.4%	1.7 2.9%	3.3 2.8%	0 NaN	2.2 NaN
Any Pain in extremity	6.6 10.8%	6.8 11.5%	9.8 8.2%	13.3 NaN	11.0 NaN
Grade ≥3 Pain in extremity	0 0%	1.7 2.9%	0 0%	0 NaN	0 NaN
Any Periorbital edema	18.0 29.5%	1.7 2.9%	24.6 20.5%	13.3 NaN	20.0 NaN
Grade ≥3 Periorbital edema	1.6 2.6%	0 0%	1.6 1.3%	0 NaN	1.1 NaN
Any Eyelid edema	3.3 5.4%	0 0%	4.9 4.1%	10.0 NaN	6.6 NaN
Grade ≥3 Eyelid edema	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Decreased appetite	16.4 26.9%	10.2 17.3%	18.0 15%	10.0 NaN	15.4 NaN
Grade ≥3 Decreased appetite	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Hypertension	14.8 24.3%	10.2 17.3%	19.7 16.4%	30.0 NaN	13.1 NaN
Grade ≥3 Hypertension	4.9 8%	0 0%	4.9 4.1%	6.7 NaN	5.5 NaN
Any Upper respiratory tract infection	1.6 2.6%	0 0%	11.5 9.6%	3.3 NaN	8.8 NaN
Grade ≥3 Upper respiratory tract infection	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Cough	4.9 8%	5.1 8.6%	6.6 5.5%	10.0 NaN	7.7 NaN
Grade ≥3 Cough	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Dyspnea	1.6 2.6%	0 0%	4.9 4.1%	10.0 NaN	7.7 NaN
Grade ≥3 Dyspnea	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Insomnia	4.9 8%	3.4 5.8%	4.9 4.1%	10.0 NaN	6.6 NaN
Grade ≥3 Insomnia	0 0%	0 0%	0 0%	0 NaN	0 NaN
Any Rash	14.8 24.3%	5.1 8.6%	27.9 23.3%	23.3 NaN	26.4 NaN
Grade ≥3 Rash	1.6 2.6%	0 0%	1.6 1.3%	0 NaN	1.1 NaN

12. Other Pre-specified Outcome

Title	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 by Week 49
Description	Complete (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.
Time Frame	By Week 49

Outcome Measure Data

Analysis Population Description

Best overall response was assessed in the ITT population.

Arm/Group Title	Pexidartinib Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2	All Pexidartinib Treated
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose. Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Measure Participants	61	30	91
Complete Response (CR)	24.6 40.3%	23.3 39.5%	24.2 20.2%
Partial Response (PR)	29.5 48.4%	30.0 50.8%	29.7 24.8%
Response (CR or PR)	54.1 88.7%	53.3 90.3%	53.8 44.8%

13. Other Pre-specified Outcome

Title	Mean Change From Baseline For Range of Motion (ROM) Score in Participants Receiving Pexidartinib Compared With Those on Placebo by Week 49
Description	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.
Time Frame	By Week 49

Outcome Measure Data

Analysis Population Description

Range of Motion (ROM) was assessed in the ITT population.

Arm/Group Title	Pexidartinib Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2	All Pexidartinib Treated
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose. Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Measure Participants	61	30	91
Baseline	62.5 (24.8)	66.5 (22.9)	63.8 (24.2)
Week 25	15.6 (14.9)	13.1 (12.9)	14.8 (14.2)
Week 49	14.4 (19.5)	12.0 (13.4)	13.4 (17.3)

14. Other Pre-specified Outcome

Title	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 by Week 49
Description	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.
Time Frame	By Week 49

Outcome Measure Data

Analysis Population Description

Physical function was assessed in the ITT population.

Arm/Group Title	Pexidartinib Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2	All Pexidartinib Treated
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose. Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Measure Participants	61	30	91
Week 25	3.6 (4.9)	4.9 (6.3)	4.0 (5.4)
Week 49	4.7 (4.4)	7.6 (6.3)	5.8 (5.2)

15. Other Pre-specified Outcome

Title	Mean Change From Baseline for Worst Stiffness Numeric Rating Scale Score (NRS) in Participants Receiving Pexidartinib Compared With Those on Placebo by Week 49
Description	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).
Time Frame	Baseline, Week 25, and Week 49

Outcome Measure Data

Analysis Population Description

Worst stiffness was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Placebo Part 1, Pexidartinib Part 2; and All Pexidartinib Treated participants. Participants who received Placebo Part 1 only or Pexidartinib Part 2 only were not analyzed.

Arm/Group Title	Pexidartinib Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2	All Pexidartinib Treated
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose. Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Measure Participants	61	30	91
Baseline	5.6 (1.7)	5.7 (2.3)	5.6 (1.9)
Week 25	-2.7 (2.2)	-3.0 (3.1)	-2.8 (2.5)
Week 49	-3.5 (1.9)	-2.2 (2.8)	-3.1 (2.3)

16. Other Pre-specified Outcome

Title	Mean Change From Baseline for Worst Pain Numeric Rating Scale Score (NRS) in Participants Receiving Pexidartinib Compared With Those on Placebo by Week 49
Description	The Brief Pain Inventory (BPI) Worst Pain 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).
Time Frame	By Week 49

Outcome Measure Data

Analysis Population Description

Worst pain was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Placebo Part 1, Pexidartinib Part 2; and All Pexidartinib Treated participants. Participants who received Placebo Part 1 only or Pexidartinib Part 2 only were not analyzed.

Arm/Group Title	Pexidartinib Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2	All Pexidartinib Treated
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose. Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Measure Participants	61	30	91
Baseline	5.6 (1.6)	5.2 (2.5)	5.5 (1.9)
Week 25	-2.7 (2.2)	-2.6 (3.1)	-2.7 (2.5)
Week 49	-3.3 (1.7)	-2.8 (3.4)	-3.2 (2.3)

17. Other Pre-specified Outcome

Title	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 by Week 49
Description	Best overall response (CR or PR) was assessed using tumor volume score (TVS) in the ITT population. Tumor Volume Score 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.
Time Frame	By Week 49

Outcome Measure Data

Analysis Population Description

Best overall response on Tumor Volume Score was assessed in the ITT population, specifically among the Pexidartinib Part 1, Pexidartinib Part 2; Placebo Part 1, Pexidartinib Part 2; and All Pexidartinib Treated participants. Participants who received Placebo Part 1 only or Pexidartinib Part 2 only were not analyzed..

Arm/Group Title	Pexidartinib Part 1 and Part 2	Placebo Part 1, Pexidartinib Part 2	All Pexidartinib Treated
Arm/Group Description	Participants received treatment of Pexidartinib,1000 mg (5 capsules per day) for 2 weeks, then 800 mg (4 capsules per day) for 22 weeks and also received Pexidartinib in Part 2 at their prescribed dose. Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	Participants received treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks in Part 1 and also received Pexidartinib in Part 2 at their prescribed dose. Placebo: Placebo capsule matching Pexidartinib capsule for oral administration Pexidartinib: Each capsule contains 200 mg of Pexidartinib for oral administration.	All participants who received Pexidartinib in Part 1 and Part 2 as well as those who only received Pexidartinib in Part 2.
Measure Participants	61	30	91
Number [Percentage of participants]	63.9 104.8%	66.7 113.1%	64.8 54%

Adverse Events

Time Frame	Adverse events were monitored throughout the study from the time the participant signed the informed consent form to 28 days after the final treatment dose, up to 71 months.
Arm/Group Title	Pexidartinib (Part 1)		Placebo (Part 1)		Pexidartinib (Parts 1 and 2)		Placebo (Part 1), Crossover Pexidartinib (Part 2)		All Pexidartinib Treated
Arm/Group Description	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 Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration		Participants received blinded treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks Placebo: Placebo capsule matching pexidartinib capsule for oral administration		Participants received pexidartinib in Part 1 and in Part 2 at their prescribed dose Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration		Participants received placebo in Part 1 and pexidartinib in Part 2 at their prescribed dose Pexidartinib: Each capsule contains 200 mg of pexidartinib for oral administration Placebo: Placebo capsule matching pexidartinib capsule for oral administration		All participants who received pexidartinib in Part 1 and Part 2 (placebo crossed over to pexidartinib)
All Cause Mortality
	Pexidartinib (Part 1)		Placebo (Part 1)		Pexidartinib (Parts 1 and 2)		Placebo (Part 1), Crossover Pexidartinib (Part 2)		All Pexidartinib Treated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Serious Adverse Events
	Pexidartinib (Part 1)		Placebo (Part 1)		Pexidartinib (Parts 1 and 2)		Placebo (Part 1), Crossover Pexidartinib (Part 2)		All Pexidartinib Treated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/61 (13.1%)		1/59 (1.7%)		12/61 (19.7%)		9/30 (30%)		21/91 (23.1%)
Cardiac disorders
Cardiac arrest	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Gastrointestinal disorders
Abdominal pain	0/61 (0%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
General disorders
Local swelling	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Non-cardiac chest pain	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Hepatobiliary disorders
Hepatoxicity	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Liver disorder	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Hepatotoxicity	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Infections and infestations
Hepatitis A	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Hepatitis E	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Lymphangitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Bronchopneumonia	0/61 (0%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Paronychia	0/61 (0%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Injury, poisoning and procedural complications
Joint injury	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Post procedural complication	0/61 (0%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Rib fracture	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Spinal fracture	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Wound dehiscence	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Investigations
Transaminases increased	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Liver function test abnormal	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Hepatic enzyme abnormal	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Blood bilirubin increased	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Musculoskeletal and connective tissue disorders
Neck pain	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Osteoarthritis	0/61 (0%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Spondylolisthesis	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenosquamous carcinoma of the cervix	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Rectal adenocarcinoma	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Endometrial cancer	0/61 (0%)		1/59 (1.7%)		0/61 (0%)		0/30 (0%)		0/91 (0%)
Squamous cell carcinoma of skin	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Lipoma	0/61 (0%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Rectal cancer stage II	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Squamous cell carcinoma	0/61 (0%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Nervous system disorders
Migraine	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/30 (3.3%)		1/91 (1.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/61 (0%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Skin and subcutaneous tissue disorders
Rash papular	0/61 (0%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Rash	1/61 (1.6%)		0/59 (0%)		1/61 (1.6%)		0/30 (0%)		1/91 (1.1%)
Other (Not Including Serious) Adverse Events
	Pexidartinib (Part 1)		Placebo (Part 1)		Pexidartinib (Parts 1 and 2)		Placebo (Part 1), Crossover Pexidartinib (Part 2)		All Pexidartinib Treated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/61 (98.4%)		55/59 (93.2%)		61/61 (100%)		30/30 (100%)		91/91 (100%)
Blood and lymphatic system disorders
Anaemia	3/61 (4.9%)	3	1/59 (1.7%)	2	7/61 (11.5%)	12	1/30 (3.3%)	1	8/91 (8.8%)	13
Neutropenia	3/61 (4.9%)	3	0/59 (0%)	0	4/61 (6.6%)	13	2/30 (6.7%)	3	6/91 (6.6%)	16
Leukopenia	2/61 (3.3%)	2	0/59 (0%)	0	4/61 (6.6%)	7	2/30 (6.7%)	10	6/91 (6.6%)	17
Thrombocytopenia	2/61 (3.3%)	2	0/59 (0%)	0	2/61 (3.3%)	2	2/30 (6.7%)	5	4/91 (4.4%)	7
Cardiac disorders
Bradycardia	0/61 (0%)	0	0/59 (0%)	0	0/61 (0%)	0	2/30 (6.7%)	3	2/91 (2.2%)	3
Palpitations	2/61 (3.3%)	2	0/59 (0%)	0	4/61 (6.6%)	5	0/30 (0%)	0	4/91 (4.4%)	5
Tachycardia	0/61 (0%)	0	0/59 (0%)	0	1/61 (1.6%)	3	2/30 (6.7%)	2	3/91 (3.3%)	5
Ear and labyrinth disorders
Tinnitus	1/61 (1.6%)	1	0/59 (0%)	0	2/61 (3.3%)	2	3/30 (10%)	6	5/91 (5.5%)	8
Vertigo	1/61 (1.6%)	1	0/59 (0%)	0	4/61 (6.6%)	4	4/30 (13.3%)	4	8/91 (8.8%)	8
Eye disorders
Periorbital oedema	11/61 (18%)	13	1/59 (1.7%)	1	17/61 (27.9%)	23	5/30 (16.7%)	6	22/91 (24.2%)	29
Eye oedema	6/61 (9.8%)	6	2/59 (3.4%)	2	6/61 (9.8%)	6	0/30 (0%)	0	6/91 (6.6%)	6
Eyelid oedema	0/61 (0%)	0	0/59 (0%)	0	3/61 (4.9%)	5	3/30 (10%)	4	6/91 (6.6%)	9
Vision blurred	0/61 (0%)	0	0/59 (0%)	0	5/61 (8.2%)	5	2/30 (6.7%)	3	7/91 (7.7%)	8
Lacrimation increased	3/61 (4.9%)	3	0/59 (0%)	0	4/61 (6.6%)	4	1/30 (3.3%)	1	5/91 (5.5%)	5
Gastrointestinal disorders
Nausea	23/61 (37.7%)	40	24/59 (40.7%)	27	28/61 (45.9%)	66	7/30 (23.3%)	10	35/91 (38.5%)	76
Diarrhea	13/61 (21.3%)	17	15/59 (25.4%)	18	19/61 (31.1%)	34	10/30 (33.3%)	23	29/91 (31.9%)	57
Vomiting	12/61 (19.7%)	16	3/59 (5.1%)	3	16/61 (26.2%)	23	3/30 (10%)	3	19/91 (20.9%)	26
Abdominal pain	10/61 (16.4%)	12	6/59 (10.2%)	8	13/61 (21.3%)	15	3/30 (10%)	3	16/91 (17.6%)	18
Constipation	7/61 (11.5%)	8	3/59 (5.1%)	3	10/61 (16.4%)	13	3/30 (10%)	5	13/91 (14.3%)	18
Dry mouth	6/61 (9.8%)	6	2/59 (3.4%)	2	8/61 (13.1%)	10	4/30 (13.3%)	4	12/91 (13.2%)	14
Stomatitis	4/61 (6.6%)	4	1/59 (1.7%)	2	5/61 (8.2%)	5	3/30 (10%)	5	8/91 (8.8%)	10
Abdominal pain upper	0/61 (0%)	0	4/59 (6.8%)	4	3/61 (4.9%)	3	2/30 (6.7%)	2	5/91 (5.5%)	5
General disorders
Fatigue	33/61 (54.1%)	49	21/59 (35.6%)	26	35/61 (57.4%)	57	8/30 (26.7%)	13	43/91 (47.3%)	70
Face oedema	8/61 (13.1%)	8	1/59 (1.7%)	1	9/61 (14.8%)	11	6/30 (20%)	13	15/91 (16.5%)	24
Oedema peripheral	8/61 (13.1%)	9	2/59 (3.4%)	2	15/61 (24.6%)	18	9/30 (30%)	11	24/91 (26.4%)	29
Asthenia	6/61 (9.8%)	7	3/59 (5.1%)	5	9/61 (14.8%)	16	7/30 (23.3%)	18	16/91 (17.6%)	34
Pyrexia	4/61 (6.6%)	4	1/59 (1.7%)	1	8/61 (13.1%)	8	6/30 (20%)	6	14/91 (15.4%)	14
Influenza like illness	0/61 (0%)	0	0/59 (0%)	0	5/61 (8.2%)	6	1/30 (3.3%)	1	6/91 (6.6%)	7
Chest pain	0/61 (0%)	0	0/59 (0%)	0	1/61 (1.6%)	1	2/30 (6.7%)	2	3/91 (3.3%)	3
Malaise	0/61 (0%)	0	0/59 (0%)	0	1/61 (1.6%)	1	2/30 (6.7%)	3	3/91 (3.3%)	4
Peripheral swelling	0/61 (0%)	0	1/59 (1.7%)	1	0/61 (0%)	0	2/30 (6.7%)	2	2/91 (2.2%)	2
Infections and infestations
Nasopharyngitis	4/61 (6.6%)	5	3/59 (5.1%)	3	5/61 (8.2%)	7	2/30 (6.7%)	2	7/91 (7.7%)	9
Upper respiratory tract infection	0/61 (0%)	0	0/59 (0%)	0	8/61 (13.1%)	11	2/30 (6.7%)	2	10/91 (11%)	13
Sinusitis	0/61 (0%)	0	0/59 (0%)	0	5/61 (8.2%)	9	1/30 (3.3%)	1	6/91 (6.6%)	10
Cellulitis	0/61 (0%)	0	0/59 (0%)	0	1/61 (1.6%)	1	3/30 (10%)	3	4/91 (4.4%)	4
Cystitis	0/61 (0%)	0	1/59 (1.7%)	1	0/61 (0%)	0	2/30 (6.7%)	3	2/91 (2.2%)	3
Influenza	0/61 (0%)	0	2/59 (3.4%)	2	2/61 (3.3%)	3	4/30 (13.3%)	5	6/91 (6.6%)	8
Urinary tract infection	0/61 (0%)	0	4/59 (6.8%)	5	2/61 (3.3%)	2	2/30 (6.7%)	6	4/91 (4.4%)	8
Herpes zoster	0/61 (0%)	0	0/59 (0%)	0	0/61 (0%)	0	2/30 (6.7%)	2	2/91 (2.2%)	2
Investigations
Aspartate aminotransferase increased	24/61 (39.3%)	48	0/59 (0%)	0	28/61 (45.9%)	63	6/30 (20%)	11	34/91 (37.4%)	74
Alanine aminotransferase increased	17/61 (27.9%)	44	1/59 (1.7%)	1	19/61 (31.1%)	53	7/30 (23.3%)	13	26/91 (28.6%)	66
Blood alkaline phosphatase increased	9/61 (14.8%)	26	0/59 (0%)	0	9/61 (14.8%)	30	1/30 (3.3%)	1	10/91 (11%)	31
Blood lactate dehydrogenase increased	7/61 (11.5%)	12	0/59 (0%)	0	7/61 (11.5%)	17	3/30 (10%)	6	10/91 (11%)	23
White blood cell count decreased	0/61 (0%)	0	1/59 (1.7%)	1	6/61 (9.8%)	11	1/30 (3.3%)	2	7/91 (7.7%)	13
Weight increased	0/61 (0%)	0	0/59 (0%)	0	3/61 (4.9%)	4	4/30 (13.3%)	4	7/91 (7.7%)	8
Blood bilirubin increased	0/61 (0%)	0	1/59 (1.7%)	2	4/61 (6.6%)	8	1/30 (3.3%)	1	5/91 (5.5%)	9
Blood creatinine phosphokinase increased	0/61 (0%)	0	0/59 (0%)	0	6/61 (9.8%)	16	4/30 (13.3%)	27	10/91 (11%)	43
Blood triglycerides increased	1/61 (1.6%)	1	0/59 (0%)	0	1/61 (1.6%)	3	2/30 (6.7%)	2	3/91 (3.3%)	5
Metabolism and nutrition disorders
Decreased appetite	10/61 (16.4%)	13	6/59 (10.2%)	6	11/61 (18%)	15	3/30 (10%)	4	14/91 (15.4%)	19
Hypercholesterolemia	5/61 (8.2%)	8	0/59 (0%)	0	7/61 (11.5%)	20	4/30 (13.3%)	7	11/91 (12.1%)	27
Fluid retention	0/61 (0%)	0	0/59 (0%)	0	3/61 (4.9%)	6	2/30 (6.7%)	5	5/91 (5.5%)	11
Hyperglycemia	0/61 (0%)	0	1/59 (1.7%)	1	1/61 (1.6%)	1	2/30 (6.7%)	2	3/91 (3.3%)	3
Hypophosphataemia	3/61 (4.9%)	3	1/59 (1.7%)	1	3/61 (4.9%)	6	2/30 (6.7%)	3	5/91 (5.5%)	9
Hypertriglyceridaemia	0/61 (0%)	0	4/59 (6.8%)	5	2/61 (3.3%)	4	2/30 (6.7%)	3	4/91 (4.4%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	14/61 (23%)	17	15/59 (25.4%)	18	19/61 (31.1%)	29	15/30 (50%)	33	34/91 (37.4%)	62
Pain in extremity	4/61 (6.6%)	6	3/59 (5.1%)	3	9/61 (14.8%)	11	6/30 (20%)	17	15/91 (16.5%)	28
Back pain	0/61 (0%)	0	0/59 (0%)	0	6/61 (9.8%)	7	4/30 (13.3%)	8	10/91 (11%)	15
Myalgia	1/61 (1.6%)	1	2/59 (3.4%)	2	2/61 (3.3%)	2	4/30 (13.3%)	7	6/91 (6.6%)	9
Muscle spasms	2/61 (3.3%)	2	1/59 (1.7%)	1	4/61 (6.6%)	6	1/30 (3.3%)	1	5/91 (5.5%)	7
neck pain	1/61 (1.6%)	1	1/59 (1.7%)	1	1/61 (1.6%)	1	4/30 (13.3%)	5	5/91 (5.5%)	6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	4/61 (6.6%)	7	4/59 (6.8%)	6	4/61 (6.6%)	7	2/30 (6.7%)	2	6/91 (6.6%)	9
Nervous system disorders
Dysgeusia	15/61 (24.6%)	24	1/59 (1.7%)	1	18/61 (29.5%)	29	7/30 (23.3%)	10	25/91 (27.5%)	39
Headache	11/61 (18%)	16	11/59 (18.6%)	15	15/61 (24.6%)	25	6/30 (20%)	8	21/91 (23.1%)	33
Dizziness	6/61 (9.8%)	7	9/59 (15.3%)	12	10/61 (16.4%)	14	5/30 (16.7%)	5	15/91 (16.5%)	19
Paresthesia	0/61 (0%)	0	1/59 (1.7%)	1	6/61 (9.8%)	7	3/30 (10%)	6	9/91 (9.9%)	13
Memory impairment	0/61 (0%)	0	1/59 (1.7%)	1	2/61 (3.3%)	2	3/30 (10%)	7	5/91 (5.5%)	9
Neuropathy peripheral	0/61 (0%)	0	0/59 (0%)	0	4/61 (6.6%)	5	1/30 (3.3%)	1	5/91 (5.5%)	6
Hypoaesthesia	1/61 (1.6%)	1	2/59 (3.4%)	2	1/61 (1.6%)	1	3/30 (10%)	5	4/91 (4.4%)	6
Sciatica	0/61 (0%)	0	1/59 (1.7%)	1	0/61 (0%)	0	2/30 (6.7%)	2	2/91 (2.2%)	2
Psychiatric disorders
Insomnia	0/61 (0%)	0	2/59 (3.4%)	2	4/61 (6.6%)	4	3/30 (10%)	4	7/91 (7.7%)	8
Anxiety	0/61 (0%)	0	1/59 (1.7%)	1	1/61 (1.6%)	1	2/30 (6.7%)	2	3/91 (3.3%)	3
Renal and urinary disorders
Haematuria	0/61 (0%)	0	2/59 (3.4%)	2	0/61 (0%)	0	2/30 (6.7%)	2	2/91 (2.2%)	2
Respiratory, thoracic and mediastinal disorders
Cough	0/61 (0%)	0	3/59 (5.1%)	3	4/61 (6.6%)	6	5/30 (16.7%)	7	9/91 (9.9%)	13
Dyspnoea	0/61 (0%)	0	0/59 (0%)	0	3/61 (4.9%)	4	4/30 (13.3%)	4	7/91 (7.7%)	8
Oropharyngeal pain	0/61 (0%)	0	2/59 (3.4%)	3	4/61 (6.6%)	4	1/30 (3.3%)	1	5/91 (5.5%)	5
Skin and subcutaneous tissue disorders
Hair color changes	41/61 (67.2%)	46	2/59 (3.4%)	2	44/61 (72.1%)	53	25/30 (83.3%)	39	69/91 (75.8%)	92
Pruritis	10/61 (16.4%)	11	2/59 (3.4%)	2	10/61 (16.4%)	10	9/30 (30%)	15	19/91 (20.9%)	25
Rash	8/61 (13.1%)	9	3/59 (5.1%)	4	17/61 (27.9%)	28	8/30 (26.7%)	13	25/91 (27.5%)	41
Rash maculo-papular	6/61 (9.8%)	8	1/59 (1.7%)	1	10/61 (16.4%)	17	4/30 (13.3%)	5	14/91 (15.4%)	22
Erythema	0/61 (0%)	0	0/59 (0%)	0	2/61 (3.3%)	3	6/30 (20%)	10	8/91 (8.8%)	13
Pruritis generalized	0/61 (0%)	0	0/59 (0%)	0	6/61 (9.8%)	7	5/30 (16.7%)	5	11/91 (12.1%)	12
Dry skin	0/61 (0%)	0	2/59 (3.4%)	2	5/61 (8.2%)	6	3/30 (10%)	4	8/91 (8.8%)	10
Alopecia	0/61 (0%)	0	0/59 (0%)	0	4/61 (6.6%)	4	2/30 (6.7%)	2	6/91 (6.6%)	6
Skin hypopigmentation	0/61 (0%)	0	0/59 (0%)	0	5/61 (8.2%)	7	1/30 (3.3%)	1	6/91 (6.6%)	8
Photosensitivity reaction	0/61 (0%)	0	0/59 (0%)	0	3/61 (4.9%)	3	3/30 (10%)	4	6/91 (6.6%)	7
Rash pruritic	0/61 (0%)	0	1/59 (1.7%)	1	1/61 (1.6%)	1	2/30 (6.7%)	3	3/91 (3.3%)	4
Dermatitis	0/61 (0%)	0	0/59 (0%)	0	0/61 (0%)	0	2/30 (6.7%)	3	2/91 (2.2%)	3
Vascular disorders
Hypertension	9/61 (14.8%)	15	6/59 (10.2%)	6	14/61 (23%)	24	12/30 (40%)	21	26/91 (28.6%)	45
Hypotension	0/61 (0%)	0	0/59 (0%)	0	0/61 (0%)	0	2/30 (6.7%)	2	2/91 (2.2%)	2

Limitations/Caveats

Enrollment was stopped on 30 Sep 2016; no new participants received the study drug. After Part 1, those who wished to continue were un-blinded; those on placebo were discontinued.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.