Phase 3 Study of Pexidartinib for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS)
- Conditions
- Pigmented Villonodular SynovitisGiant Cell Tumors of the Tendon SheathTenosynovial Giant Cell Tumor
- Interventions
- Drug: Placebo
- Registration Number
- NCT02371369
- Lead Sponsor
- Daiichi Sankyo
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part 2 - Placebo-Pexidartinib Placebo Participants received placebo in Part 1 and pexidartinib in Part 2 at their prescribed dose Part 1 - Placebo 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 Part 1 - Pexidartinib 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 Part 2 - All Pexidartinib Pexidartinib Participants received pexidartinib in Part 1 and in Part 2 at their prescribed dose Part 2 - Placebo-Pexidartinib Pexidartinib Participants received placebo in Part 1 and pexidartinib in Part 2 at their prescribed dose
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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).
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.
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.
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.
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.
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.
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).
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.
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.
Trial Locations
- Locations (38)
University of Southern California
🇺🇸Los Angeles, California, United States
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
Institut Gustave Roussy
🇫🇷Villejuif, France
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
: Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
OHSU Knight Cancer Institute
🇺🇸Portland, Oregon, United States
Military Hospital-State Health Center
🇭🇺Budapest, Hungary
University College Hospital
🇬🇧London, United Kingdom
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Peter MacCallum Cancer Centre
🇦🇺East Melbourne, Victoria, Australia
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Herlev Hospital
🇩🇰Herlev, Denmark
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
UCLA Medical Center
🇺🇸Santa Monica, California, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Chris O'Brien Lifehouse
🇦🇺Sydney, New South Wales, Australia
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Centre Leon Bérard
🇫🇷Lyon, France
HELIOS Klinikum Berlin-Buch
🇩🇪Berlin, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
The Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
Istituto Ortopedico Rizzoli
🇮🇹Bologna, BO, Italy
Istituto Nazionale Tumori-Fondazione IRCCS
🇮🇹Milano, MI, Italy
Radboud Univ. Medical Center
🇳🇱Nijmegen, Netherlands
Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie
🇵🇱Warszawa, Poland
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
MD Anderson Cancer Center at Cooper
🇺🇸Camden, New Jersey, United States