Last reviewed · How we verify

NCT02371369: ENLIVEN

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

Completed Phase 3 Results posted Last updated 11 May 2022
What this trial tests

Phase 3 trial testing Pexidartinib in Pigmented Villonodular Synovitis in 120 participants. Completed in 30 April 2021.

Timeline
11 May 2015
Primary endpoint
27 March 2017
30 April 2021

Quick facts

Lead sponsorDaiichi Sankyo
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingquadruple
Primary purposetreatment
Enrollment120
Start date11 May 2015
Primary completion27 March 2017
Estimated completion30 April 2021
Sites39 locations across Denmark, France, Italy, Netherlands, United Kingdom, Germany, Hungary, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Daiichi Sankyo — full company profile →

Who can join

18 and older, any sex, with Pigmented Villonodular Synovitis or Giant Cell Tumors of the Tendon Sheath. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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.

Complete Response (CR)
GroupValue95% CI
Pexidartinib Part 114.8
Placebo Part 10
Partial Response (PR)
GroupValue95% CI
Pexidartinib Part 124.6
Placebo Part 10
Response (CR or PR)
GroupValue95% CI
Pexidartinib Part 139.3
Placebo Part 10
Mean Change From Baseline For Range of Motion (ROM) Score in Participants Receiving Pexidartinib Compared With Those on Placebo Up to Week 25 Secondary · 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.

Baseline
GroupValue95% CI
Pexidartinib Part 162.5± 3.2
Placebo Part 162.9± 2.9
Week 13
GroupValue95% CI
Pexidartinib Part 113.0± 2.3
Placebo Part 14.8± 2.6
Week 25
GroupValue95% CI
Pexidartinib Part 115.1± 2.1
Placebo Part 16.2± 2.4
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 Secondary · 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

Complete Response (CR)
GroupValue95% CI
Pexidartinib Part 14.9
Placebo Part 10
Partial Response (PR)
GroupValue95% CI
Pexidartinib Part 150.8
Placebo Part 10
Response (CR or PR)
GroupValue95% CI
Pexidartinib Part 155.7
Placebo Part 10
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 Secondary · 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.

Week 9
GroupValue95% CI
Pexidartinib Part 12.8± 1.0
Placebo Part 1-0.4± 0.8
Week 17
GroupValue95% CI
Pexidartinib Part 13.2± 1.1
Placebo Part 10.2± 1.0
Week 25
GroupValue95% CI
Pexidartinib Part 14.1± 1.1
Placebo Part 1-0.9± 1.0
Mean Change From Baseline for Worst Stiffness Numeric Rating Scale Score (NRS) in Participants Receiving Pexidartinib Compared With Those on Placebo Up to Week 25 Secondary · 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).

Baseline
GroupValue95% CI
Pexidartinib Part 15.6± 0.2
Placebo Part 15.9± 0.3
Week 9
GroupValue95% CI
Pexidartinib Part 1-1.5± 0.3
Placebo Part 1-0.5± 0.3
Week 17
GroupValue95% CI
Pexidartinib Part 1-2.4± 0.3
Placebo Part 1-0.4± 0.3
Week 25
GroupValue95% CI
Pexidartinib Part 1-2.5± 0.3
Placebo Part 1-0.3± 0.3
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 Secondary · 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).

GroupValue95% CI
Pexidartinib Part 131.1
Placebo Part 115.3
Number of Responders to Pexidartinib With and Without Disease Progression Secondary · 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.

Number of responses
GroupValue95% CI
Pexidartinib Part 1 and Part 223
Placebo Part 1, Pexidartinib Part 212
All Pexidartinib Treated35
Week 12 (Day 84); Without disease progression
GroupValue95% CI
Pexidartinib Part 1 and Part 223
Placebo Part 1, Pexidartinib Part 212
All Pexidartinib Treated35
Week 12 (Day 84); With disease progression
GroupValue95% CI
Pexidartinib Part 1 and Part 20
Placebo Part 1, Pexidartinib Part 20
All Pexidartinib Treated0
Week 24 (Day 168); Without disease progression
GroupValue95% CI
Pexidartinib Part 1 and Part 223
Placebo Part 1, Pexidartinib Part 212
All Pexidartinib Treated35
Week 24 (Day 168); With disease progression
GroupValue95% CI
Pexidartinib Part 1 and Part 20
Placebo Part 1, Pexidartinib Part 20
All Pexidartinib Treated0
Week 48 (Day 336); Without disease progression
GroupValue95% CI
Pexidartinib Part 1 and Part 215
Placebo Part 1, Pexidartinib Part 29
All Pexidartinib Treated24
Week 48 (Day 336); With disease progression
GroupValue95% CI
Pexidartinib Part 1 and Part 21
Placebo Part 1, Pexidartinib Part 20
All Pexidartinib Treated1
Week 72 (Day 504); Without disease progression
GroupValue95% CI
Pexidartinib Part 1 and Part 29
Placebo Part 1, Pexidartinib Part 23
All Pexidartinib Treated12
Number of Responders to Pexidartinib With and Without Disease Progression Based on Tumor Volume Score Secondary · 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.

Number of responders
GroupValue95% CI
Pexidartinib in Part 1 and Part 234
Placebo Part 1, Pexidartinib Part 218
All Pexidartinib Treated52
Week 12 (Day 84); Without disease progression
GroupValue95% CI
Pexidartinib in Part 1 and Part 233
Placebo Part 1, Pexidartinib Part 218
All Pexidartinib Treated51
Week 12 (Day 84); With disease progression
GroupValue95% CI
Pexidartinib in Part 1 and Part 20
Placebo Part 1, Pexidartinib Part 20
All Pexidartinib Treated0
Week 24 (Day 168); Without disease progression
GroupValue95% CI
Pexidartinib in Part 1 and Part 232
Placebo Part 1, Pexidartinib Part 218
All Pexidartinib Treated50
Week 24 (Day 168); With disease progression
GroupValue95% CI
Pexidartinib in Part 1 and Part 20
Placebo Part 1, Pexidartinib Part 20
All Pexidartinib Treated0
Week 48 (Day 336); Without disease progression
GroupValue95% CI
Pexidartinib in Part 1 and Part 222
Placebo Part 1, Pexidartinib Part 213
All Pexidartinib Treated35
Week 48 (Day 336); With disease progression
GroupValue95% CI
Pexidartinib in Part 1 and Part 23
Placebo Part 1, Pexidartinib Part 21
All Pexidartinib Treated4
Week 72 (Day 504); Without disease progression
GroupValue95% CI
Pexidartinib in Part 1 and Part 213
Placebo Part 1, Pexidartinib Part 23
All Pexidartinib Treated16
Duration of Response (DOR) Based on RECIST 1.1 Secondary · 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.

GroupValue95% CI
Pexidartinib Part 1 and Part 2NA31.01 – NA
Placebo Part 1, Pexidartinib Part 2NA39.0 – NA
Duration of Response (DOR) Based on Tumor Volume Score (TVS) Secondary · 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.

GroupValue95% CI
Pexidartinib Part 1 and Part 252.7038.60 – NA
Placebo Part 1, Pexidartinib Part 2NANA – NA
Percentage of Participants Reporting Frequent (≥10%) Treatment-Emergent Adverse Events by Preferred Term Secondary · 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.

Any Hair color changes
GroupValue95% CI
Pexidartinib Part 167.2
Placebo Part 13.4
Pexidartinib Part 1 and Part 273.8
Placebo Part 1, Pexidartinib Part 283.3
All Pexidartinib Treated76.9
Grade ≥3 Hair color changes
GroupValue95% CI
Pexidartinib Part 10
Placebo Part 10
Pexidartinib Part 1 and Part 20
Placebo Part 1, Pexidartinib Part 20
All Pexidartinib Treated0
Any Pruritis
GroupValue95% CI
Pexidartinib Part 19.8
Placebo Part 13.4
Pexidartinib Part 1 and Part 216.4
Placebo Part 1, Pexidartinib Part 220.0
All Pexidartinib Treated17.6
Grade ≥3 Pruritis
GroupValue95% CI
Pexidartinib Part 10
Placebo Part 10
Pexidartinib Part 1 and Part 21.6
Placebo Part 1, Pexidartinib Part 20
All Pexidartinib Treated1.1
Any Rash maculopapular
GroupValue95% CI
Pexidartinib Part 19.8
Placebo Part 11.7
Pexidartinib Part 1 and Part 214.8
Placebo Part 1, Pexidartinib Part 210.0
All Pexidartinib Treated13.2
Grade ≥3 Rash maculopapular
GroupValue95% CI
Pexidartinib Part 10
Placebo Part 10
Pexidartinib Part 1 and Part 21.6
Placebo Part 1, Pexidartinib Part 20
All Pexidartinib Treated1.1
Any Pruritis generalized
GroupValue95% CI
Pexidartinib Part 18.2
Placebo Part 10
Pexidartinib Part 1 and Part 28.2
Placebo Part 1, Pexidartinib Part 210.0
All Pexidartinib Treated8.8
Grade ≥3 Pruritis generalized
GroupValue95% CI
Pexidartinib Part 10
Placebo Part 10
Pexidartinib Part 1 and Part 20
Placebo Part 1, Pexidartinib Part 20
All Pexidartinib Treated0
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 Secondary · 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.

Complete Response (CR)
GroupValue95% CI
Pexidartinib Part 1 and Part 224.6
Placebo Part 1, Pexidartinib Part 223.3
All Pexidartinib Treated24.2
Partial Response (PR)
GroupValue95% CI
Pexidartinib Part 1 and Part 229.5
Placebo Part 1, Pexidartinib Part 230.0
All Pexidartinib Treated29.7
Response (CR or PR)
GroupValue95% CI
Pexidartinib Part 1 and Part 254.1
Placebo Part 1, Pexidartinib Part 253.3
All Pexidartinib Treated53.8

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pexidartinib (Part 1)
Serious: 8/61 (13%)
Deaths: 0/61
Placebo (Part 1)
Serious: 1/59 (2%)
Deaths: 0/59
Pexidartinib (Parts 1 and 2)
Serious: 12/61 (20%)
Deaths: 0/61
Placebo (Part 1), Crossover Pexidartinib (Part 2)
Serious: 9/30 (30%)
Deaths: 1/30
All Pexidartinib Treated
Serious: 21/91 (23%)
Deaths: 1/91

Serious adverse events (36 terms)

ReactionSystemPexidartinib (Part 1)Placebo (Part 1)Pexidartinib (Parts 1 and 2)Placebo (Part 1), Crossove…All Pexidartinib Treated
Transaminases increasedInvestigations
Liver function test abnormalInvestigations
Hepatic enzyme abnormalInvestigations
Blood bilirubin increasedInvestigations
Adenosquamous carcinoma of the cervixNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal adenocarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skinNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Cardiac arrestCardiac disorders
AsthmaRespiratory, thoracic and mediastinal disorders
MigraineNervous system disorders
Local swellingGeneral disorders
Non-cardiac chest painGeneral disorders
HepatoxicityHepatobiliary disorders
Liver disorderHepatobiliary disorders
Rash papularSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
Neck painMusculoskeletal and connective tissue disorders
Hepatitis AInfections and infestations
Hepatitis EInfections and infestations
LymphangitisInfections and infestations
LipomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer stage IINeoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Joint injuryInjury, poisoning and procedural complications
Other adverse events (89 terms — click to expand)

ReactionSystemPexidartinib (Part 1)Placebo (Part 1)Pexidartinib (Parts 1 and 2)Placebo (Part 1), Crossove…All Pexidartinib Treated
Hair color changesSkin and subcutaneous tissue disorders
FatigueGeneral disorders
NauseaGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
DiarrheaGastrointestinal disorders
HypertensionVascular disorders
Alanine aminotransferase increasedInvestigations
DysgeusiaNervous system disorders
RashSkin and subcutaneous tissue disorders
Oedema peripheralGeneral disorders
Periorbital oedemaEye disorders
HeadacheNervous system disorders
VomitingGastrointestinal disorders
PruritisSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
Abdominal painGastrointestinal disorders
Face oedemaGeneral disorders
DizzinessNervous system disorders
Pain in extremityMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
Dry mouthGastrointestinal disorders
Pruritis generalizedSkin and subcutaneous tissue disorders
HypercholesterolemiaMetabolism and nutrition disorders
Blood alkaline phosphatase increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Blood creatinine phosphokinase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
Upper respiratory tract infectionInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
ParesthesiaNervous system disorders
AnaemiaBlood and lymphatic system disorders
VertigoEar and labyrinth disorders
StomatitisGastrointestinal disorders
ErythemaSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
InsomniaPsychiatric disorders

Most-reported serious reactions: Transaminases increased, Liver function test abnormal, Hepatic enzyme abnormal, Blood bilirubin increased, Adenosquamous carcinoma of the cervix, Rectal adenocarcinoma, Endometrial cancer, Squamous cell carcinoma of skin.

Data from ClinicalTrials.gov NCT02371369 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications.
    Lin Y, Xu J, Lan H. · · 2019 · cited 1078× · PMID 31300030 · DOI 10.1186/s13045-019-0760-3
  2. Targeting Tumor Microenvironment for Cancer Therapy.
    Roma-Rodrigues C, Mendes R, Baptista PV, Fernandes AR. · · 2019 · cited 865× · PMID 30781344 · DOI 10.3390/ijms20040840
  3. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy.
    Cannarile MA, Weisser M, Jacob W, Jegg AM, et al · · 2017 · cited 796× · PMID 28716061 · DOI 10.1186/s40425-017-0257-y
  4. Progress in tumor-associated macrophage (TAM)-targeted therapeutics.
    Ngambenjawong C, Gustafson HH, Pun SH. · · 2017 · cited 659× · PMID 28449873 · DOI 10.1016/j.addr.2017.04.010
  5. Targeting macrophages in cancer immunotherapy.
    Duan Z, Luo Y. · · 2021 · cited 462× · PMID 33767177 · DOI 10.1038/s41392-021-00506-6
  6. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage.
    Ushach I, Zlotnik A. · · 2016 · cited 405× · PMID 27354413 · DOI 10.1189/jlb.3ru0316-144r
  7. Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets.
    Tie Y, Tang F, Wei YQ, Wei XW. · · 2022 · cited 386× · PMID 35585567 · DOI 10.1186/s13045-022-01282-8
  8. Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial.
    Tap WD, Gelderblom H, Palmerini E, Desai J, et al · · 2019 · cited 354× · PMID 31229240 · DOI 10.1016/s0140-6736(19)30764-0

Verify or expand the search:

Other trials of Pexidartinib

Trials testing the same drug.

Other Daiichi Sankyo trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02371369.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing