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

Primary Purpose

Pigmented Villonodular Synovitis, Giant Cell Tumors of the Tendon Sheath, Tenosynovial Giant Cell Tumor

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pexidartinib
Placebo
Sponsored by
Daiichi Sankyo, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pigmented Villonodular Synovitis focused on measuring PLX3397, Pexidartinib, Colony Stimulating Factor 1 Receptor (CSF-1R) inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  1. Age ≥ 18 years.
  2. A diagnosis of PVNS or GCT-TS (i) that has been histologically confirmed either by a pathologist at the treating institution or a central pathologist, and (ii) where surgical resection would be associated with potentially worsening functional limitation or severe morbidity (locally advanced disease), with morbidity determined consensually by qualified personnel (eg, two surgeons or a multi-disciplinary tumor board).
  3. Measurable disease of at least 2 cm and otherwise based on RECIST 1.1, assessed from MRI scans by a central radiologist.
  4. Symptomatic disease because of active PVNS or GCT-TS, defined as one or more of the following:

    1. a worst pain of at least 4 at any time during the week preceding the Screening Visit (based on scale of 0 to 10, with 10 representing "pain as bad as you can imagine").
    2. a worst stiffness of at least 4 at any time during the week preceding the Screening Visit (based on a scale of 0 to 10, with 10 representing "stiffness as bad as you can imagine").
  5. Stable prescription of analgesic regimen during the 2 weeks prior to randomization.
  6. During the 2 weeks prior to randomization, at least 4 of 7 consecutive days of Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) items and Worst Stiffness NRS items completed correctly.
  7. Women of childbearing potential must have a negative serum pregnancy test within the 14-day period prior to randomization. (Where demanded by local regulations, this test may be required within 72 hours of randomization.)
  8. Males and females of childbearing potential are permitted in the study so long as they consent to avoid getting their partner pregnant or becoming pregnant, respectively, by using a highly effective contraception method, as described below, throughout the study and for up to 90 days after completion. Highly effective methods of contraception include: intra-uterine device (non-hormonal or hormonal), bilateral tubal occlusion, vasectomy, sexual abstinence, or barrier methods (eg, condom, diaphragm) used in combination with hormonal methods associated with inhibition of ovulation. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year. Women who have documentation of at least 12 months of spontaneous amenorrhea and have a follicle stimulating hormone (FSH) level > 40 milli-International units (mIU/mL) will be considered postmenopausal.
  9. Adequate hematologic, hepatic, and renal function, defined by:

    • Absolute neutrophil count ≥ 1.5 × 10^9/L
    • aspartate aminotransferase/alanine (AST/ALT) ≤ 1.5 × upper limit of normal (ULN)
    • Hemoglobin > 10 g/dL
    • Total bilirubin ≤ 1.5 × ULN
    • Platelet count ≥ 100 × 10^9/L
    • Serum creatinine ≤ 1.5 × ULN
  10. Willingness and ability to complete the Worst Pain NRS item, Worst Stiffness NRS item, Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale, and other self-assessment instruments throughout the study.
  11. Willingness and ability to use an electronic diary.
  12. Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.

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.

Sites / Locations

  • Mayo Clinic
  • University of Southern California
  • Stanford Cancer Center
  • UCLA Medical Center
  • Mayo Clinic Cancer Center
  • Sylvester Comprehensive Cancer Center
  • Moffitt Cancer Center
  • Massachusetts General Hospital
  • : Dana Farber Cancer Institute
  • Michigan Comprehensive Cancer Center
  • Mayo Clinic Cancer Center
  • Washington University School of Medicine
  • MD Anderson Cancer Center at Cooper
  • Memorial Sloan Kettering Cancer Center
  • Duke Cancer Center
  • OHSU Knight Cancer Institute
  • Vanderbilt-Ingram Cancer Center
  • Huntsman Cancer Institute
  • Seattle Cancer Care Alliance
  • Chris O'Brien Lifehouse
  • Princess Alexandra Hospital
  • Peter MacCallum Cancer Centre
  • Princess Margaret Hospital
  • McGill University Health Centre
  • Herlev Hospital
  • Centre Leon Bérard
  • Institut Gustave Roussy
  • HELIOS Klinikum Berlin-Buch
  • Universitätsklinikum Essen
  • Military Hospital-State Health Center
  • Istituto Ortopedico Rizzoli
  • Istituto Nazionale Tumori-Fondazione IRCCS
  • Leiden University Medical Center
  • Radboud Univ. Medical Center
  • Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie
  • Hospital de la Santa Creu i Sant Pau
  • Hospital Universitario Virgen del Rocío
  • University College Hospital
  • The Royal Marsden NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

Part 1 - Pexidartinib

Part 1 - Placebo

Part 2 - All Pexidartinib

Part 2 - Placebo-Pexidartinib

Arm 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

Participants received blinded treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks

Participants received pexidartinib in Part 1 and in Part 2 at their prescribed dose

Participants received placebo in Part 1 and pexidartinib in Part 2 at their prescribed dose

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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).
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).
Number of Responders to Pexidartinib With and Without Disease Progression
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.
Number of Responders to Pexidartinib With and Without Disease Progression Based on Tumor Volume Score
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.
Duration of Response (DOR) Based on RECIST 1.1
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.
Duration of Response (DOR) Based on Tumor Volume Score (TVS)
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.
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.

Full Information

First Posted
February 19, 2015
Last Updated
April 11, 2022
Sponsor
Daiichi Sankyo, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02371369
Brief Title
Phase 3 Study of Pexidartinib for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS)
Acronym
ENLIVEN
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
May 11, 2015 (Actual)
Primary Completion Date
March 27, 2017 (Actual)
Study Completion Date
April 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pigmented Villonodular Synovitis, Giant Cell Tumors of the Tendon Sheath, Tenosynovial Giant Cell Tumor
Keywords
PLX3397, Pexidartinib, Colony Stimulating Factor 1 Receptor (CSF-1R) inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) in Part 1, Open-label (no masking) in Part 2
Allocation
Randomized
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1 - Pexidartinib
Arm Type
Experimental
Arm 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
Arm Title
Part 1 - Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received blinded treatment of matching placebo (5 capsules per day) for 2 weeks, then matching placebo (4 capsules per day) for 22 weeks
Arm Title
Part 2 - All Pexidartinib
Arm Type
Experimental
Arm Description
Participants received pexidartinib in Part 1 and in Part 2 at their prescribed dose
Arm Title
Part 2 - Placebo-Pexidartinib
Arm Type
Experimental
Arm Description
Participants received placebo in Part 1 and pexidartinib in Part 2 at their prescribed dose
Intervention Type
Drug
Intervention Name(s)
Pexidartinib
Other Intervention Name(s)
PLX3397, Pexidartinib hydrochloride (HCl)
Intervention Description
Each capsule contains 200 mg of pexidartinib for oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo Capsule
Intervention Description
Placebo capsule matching pexidartinib capsule for oral administration
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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)
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)
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
Other Pre-specified Outcome Measures:
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
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
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
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Age ≥ 18 years. A diagnosis of PVNS or GCT-TS (i) that has been histologically confirmed either by a pathologist at the treating institution or a central pathologist, and (ii) where surgical resection would be associated with potentially worsening functional limitation or severe morbidity (locally advanced disease), with morbidity determined consensually by qualified personnel (eg, two surgeons or a multi-disciplinary tumor board). Measurable disease of at least 2 cm and otherwise based on RECIST 1.1, assessed from MRI scans by a central radiologist. Symptomatic disease because of active PVNS or GCT-TS, defined as one or more of the following: a 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"). 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"). Stable prescription of analgesic regimen during the 2 weeks prior to randomization. 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. 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.) 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. 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 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. Willingness and ability to use an electronic diary. Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements. Exclusion Criteria Investigational drug use within 28 days of randomization. Previous use of 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. 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. Known metastatic PVNS/GCT-TS. Active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus or known active or chronic infection with human immunodeficiency virus. Known active tuberculosis. Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history that, in the Investigator's opinion, would likely interfere with the person's study participation or the interpretation of his or her results. Women who are breastfeeding. A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms (women). MRI contraindications. History of hypersensitivity to any excipients in the investigational product. Inability to swallow capsules.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Team Leader
Organizational Affiliation
Daiichi Sankyo, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259-5499
Country
United States
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Stanford Cancer Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
UCLA Medical Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
: Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
MD Anderson Cancer Center at Cooper
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Duke Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
OHSU Knight Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Chris O'Brien Lifehouse
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G2M9
Country
Canada
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A3J1
Country
Canada
Facility Name
Herlev Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Centre Leon Bérard
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
HELIOS Klinikum Berlin-Buch
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Military Hospital-State Health Center
City
Budapest
ZIP/Postal Code
H1134
Country
Hungary
Facility Name
Istituto Ortopedico Rizzoli
City
Bologna
State/Province
BO
ZIP/Postal Code
40136
Country
Italy
Facility Name
Istituto Nazionale Tumori-Fondazione IRCCS
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Radboud Univ. Medical Center
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
University College Hospital
City
London
ZIP/Postal Code
NW12BU
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust
City
London
ZIP/Postal Code
SW36JJ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
IPD Sharing Time Frame
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
IPD Sharing Access Criteria
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
IPD Sharing URL
https://vivli.org/ourmember/daiichi-sankyo/
Citations:
PubMed Identifier
36001000
Citation
Healey JH, Tap WD, Gelhorn HL, Ye X, Speck RM, Palmerini E, Stacchiotti S, Desai J, Wagner AJ, Alcindor T, Ganjoo K, Martin-Broto J, Wang Q, Shuster D, Gelderblom H, van de Sande M. Pexidartinib Provides Modest Pain Relief in Patients With Tenosynovial Giant Cell Tumor: Results From ENLIVEN. Clin Orthop Relat Res. 2023 Jan 1;481(1):107-116. doi: 10.1097/CORR.0000000000002335. Epub 2022 Aug 24.
Results Reference
derived
PubMed Identifier
33289960
Citation
Lewis JH, Gelderblom H, van de Sande M, Stacchiotti S, Healey JH, Tap WD, Wagner AJ, Pousa AL, Druta M, Lin CC, Baba HA, Choi Y, Wang Q, Shuster DE, Bauer S. Pexidartinib Long-Term Hepatic Safety Profile in Patients with Tenosynovial Giant Cell Tumors. Oncologist. 2021 May;26(5):e863-e873. doi: 10.1002/onco.13629. Epub 2020 Dec 24.
Results Reference
derived
PubMed Identifier
32755241
Citation
Tap W. ENLIVEN study: Pexidartinib for tenosynovial giant cell tumor (TGCT). Future Oncol. 2020 Sep;16(25):1875-1878. doi: 10.2217/fon-2020-0307. Epub 2020 Aug 5.
Results Reference
derived
PubMed Identifier
31229240
Citation
Tap WD, Gelderblom H, Palmerini E, Desai J, Bauer S, Blay JY, Alcindor T, Ganjoo K, Martin-Broto J, Ryan CW, Thomas DM, Peterfy C, Healey JH, van de Sande M, Gelhorn HL, Shuster DE, Wang Q, Yver A, Hsu HH, Lin PS, Tong-Starksen S, Stacchiotti S, Wagner AJ; ENLIVEN investigators. Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet. 2019 Aug 10;394(10197):478-487. doi: 10.1016/S0140-6736(19)30764-0. Epub 2019 Jun 19.
Results Reference
derived
PubMed Identifier
27041409
Citation
Gelhorn HL, Tong S, McQuarrie K, Vernon C, Hanlon J, Maclaine G, Lenderking W, Ye X, Speck RM, Lackman RD, Bukata SV, Healey JH, Keedy VL, Anthony SP, Wagner AJ, Von Hoff DD, Singh AS, Becerra CR, Hsu HH, Lin PS, Tap WD. Patient-reported Symptoms of Tenosynovial Giant Cell Tumors. Clin Ther. 2016 Apr;38(4):778-93. doi: 10.1016/j.clinthera.2016.03.008. Epub 2016 Apr 1.
Results Reference
derived

Learn more about this trial

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

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