Clinical trial NCT04488822: A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT
Official title: Multicenter, Single Arm Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With Tenosynovial Giant Cell Tumor
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Tenosynovial Giant Cell Tumor
Keywords: Tenosynovial Giant Cell Tumor
Pexidartinib
TURALIO™
PLX3397
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2020-07-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess pexidartinib in adult participants with symptomatic TGCT that is associated with severe morbidity or functional limitations and not amendable to improvement with surgery.

Detailed description: Participants with symptomatic TGCT will be administered pexidartinib 400 mg twice daily continuously with 28-day treatment cycle until criteria for discontinuation are reached. Participants who complete primary endpoint assessments may be eligible to continue receiving pexidartinib until disease progression, unacceptable toxicity, the occurrence of other termination criteria, or withdrawal from the study. Eligible participants' status will be collected every 6 months as a long term follow-up at least 2 years.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years (Age ≥ 20 years in Taiwan).
* A diagnosis of TGCT (i) that has been histologically confirmed by a pathologist and (ii) associated with severe morbidity or functional limitations and not amenable to improvement with surgery determined consensually by qualified personnel (eg, 2 surgeons or a multi-disciplinary tumor board).
* Measurable disease as defined by RECIST 1.1 (except that a minimal size of 2 cm is required), assessed from MRI scan by a central radiologist.
* Stable prescription of analgesic regimen during the 2 weeks prior to enrollment.
* Women of childbearing potential must have a negative serum pregnancy test within the 14-day period prior to enrollment (Where demanded by local regulations, this test may be required within 72 hours of enrollment).
* Females of reproductive potential should be advised to use an effective, non-hormonal method of contraception during treatment with pexidartinib and for 1 month after the last dose. Males with female partners of reproductive potential should be advised to use an effective method of contraception during treatment with pexidartinib and for 1 month after the last dose. Female partners of male participants should concurrently use effective contraceptive methods (hormonal or non-hormonal). Women of nonchildbearing 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 level \> 40 mIU/mL will be considered postmenopausal.
* Adequate hematologic, hepatic, and renal function, defined by:

  * Absolute neutrophil count ≥ 1.5 × 10\^9/L
  * Hemoglobin \> 10 g/dL
  * Platelet count ≥ 100 × 10\^9/L
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.0 × upper limit of normal (ULN)
  * Total bilirubin and direct bilirubin ≤ 1.0 × ULN
  * Alkaline phosphatase ≤ 1.0 × ULN
  * Creatinine clearance (CLcr) \> 15 mL/min
* Willingness and ability to complete the PROMIS Physical Function Scale.
* Willingness and ability to use a 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/device use within 28 days of enrolment.
* Previous use of pexidartinib or any biologic treatment targeting colony stimulating factor 1 (CSF-1) or the CSF-1 receptor; previous use of oral tyrosine kinase inhibitors are allowed (eg, imatinib or nilotinib).
* Active cancer except for tumor for which a participant is enrolled in the study, (either concurrent or within the last year of starting study drug) 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 TGCT.
* Active or chronic infection with hepatitis C or known positive hepatitis B surface antigen, or known active or chronic infection with human immunodeficiency virus.
* Active liver or biliary tract disease
* 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 a participant's study participation or the interpretation of his or her results.
* Use of strong Cytochrome P450 (CYP) 3A inducers, including St John's wort, proton pump inhibitors (PPIs), and other products known to cause hepatotoxicity.
* 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.

Primary outcomes:
measure: Overall Response Rate (ORR) of Pexidartinib Based on RECIST 1.1 of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25
timeFrame: At Week 25 postdose
Secondary outcomes:
measure: Overall Response Rate (ORR) of Pexidartinib Based on TVS of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25
timeFrame: At Week 25 postdose
measure: Mean Percent Change From Baseline for Range of Motion (ROM) Score in Participants Receiving Pexidartinib
timeFrame: At Week 25 postdose
measure: Mean Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score in Participants Receiving Pexidartinib
timeFrame: At Week 25 postdose
measure: Best Overall Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan
timeFrame: From baseline until disease progression or death (whichever occurs first), up to approximately 29 months
measure: Duration of Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan
timeFrame: Time from the date of first documented response until documented disease progression or death from any cause (whichever occurs first), up to approximately 29 months
measure: Number of Participants Reporting Frequent (≥10%) Treatment-Emergent Adverse Events by Preferred Term
timeFrame: Up to approximately 29 months
measure: Area Under the Plasma Concentration Time Curve From Time 0 to 6 Hours AUC(0-6h) in Participants Receiving Pexidartinib
timeFrame: Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)
measure: Maximum Plasma Concentration (Cmax) in Participants Receiving Pexidartinib
timeFrame: Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Participants Receiving Pexidartinib
timeFrame: Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ji Shui Tan Hospital
city: Beijing
country: China
facility: Peking University Cancer Hospital
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: