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A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT (PLX3397)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04488822
Recruitment Status : Recruiting
First Posted : July 28, 2020
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

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.

Condition or disease Intervention/treatment Phase
Tenosynovial Giant Cell Tumor Drug: Pexidartinib Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Single Arm Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With Tenosynovial Giant Cell Tumor
Actual Study Start Date : September 2, 2020
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : March 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pexidartinib Drug: Pexidartinib
400 mg twice daily for a total daily dose of 800 mg (each capsule contains 200 mg of pexidartinib for oral administration)
Other Names:
  • TURALIO™
  • PLX3397




Primary Outcome Measures :
  1. Percentage of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) Achieving Complete or Partial Response to Pexidartinib Per Response Evaluation Criteria in Solid Tumors Version 1.1 at Week 25 [ Time Frame: Week 25 postdose ]
    Complete response (CR) and partial responses (PR) will be 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 is defined as disappearance of all tumors and a PR is 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. Percentage of Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) Achieving Complete or Partial Response Based on Tumor Volume Score (TVS) by Centrally Reviewed MRI Scan [ Time Frame: Week 25 postdose ]
    Complete response (CR) and partial response (PR) will be assessed using tumor volume score (TVS). A CR is defined as disappearance of all tumors and a PR is 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.

  2. Mean Change From Baseline For Range of Motion (ROM) Score in Participants Receiving Pexidartinib [ Time Frame: Baseline up to Week 25 postdose ]
    Range of motion (ROM) of the joint will be assessed by a qualified, independent, and blinded or third-party assessors at the clinical site. Measurements will be recorded in degrees. At baseline, the plane of movement with the smallest relative value (worst) will be identified and this plane will be used for evaluating the relative change of motion subsequently. Only the plane with the worst impaired ROM at baseline will be 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 [ Time Frame: Baseline up to Week 25 postdose ]
    The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale will be used to assess physical function of the upper and lower limbs. The scale ranges 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. Best Overall Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan [ Time Frame: Baseline up to Week 157 postdose ]
    The overall number of responses and the number of participants with and without disease progression will be assessed. 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 is scored 10; a score of 0 indicates no evidence of tumor. The overall number of responses and the number of participants with and without disease progression will be assessed.

  5. Duration of Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan [ Time Frame: Baseline up to Week 157 postdose ]
    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. 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 is scored 10; a score of 0 indicates no evidence of tumor. The Duration of response of participants with and without disease progression will be assessed.

  6. Percentage of Participants Reporting Frequent (≥10%) Treatment-Emergent Adverse Events by Preferred Term [ Time Frame: After the first dose of treatment up to 28 days after the last dose, up to approximately 1 year 6 months ]
    Treatment-emergent adverse events (TEAEs) are defined as adverse events that starts or worsens 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 will be used to grade adverse events. Any Grade and Grade ≥3 (severe) TEAEs will be reported. TEAEs will be coded using MedDRA version 17.1.

  7. Area Under the Concentration Time Curve From Time 0 to 6 Hours (AUC0-6) of Pexidartinib and its Primary Metabolite ZAAD-1006a [ Time Frame: Week 1, Week 3 at predose, 0.5h, 1h, 2h, 4h, and 6h postdose, Week 5, Week 9 and Week 17 ]
  8. Maximum Serum Concentration (Cmax) of Pexidartinib and its Primary Metabolite ZAAD-1006a [ Time Frame: Week 1, Week 3 at predose, 0.5h, 1h, 2h, 4h, and 6h postdose, Week 5, Week 9 and Week 17 ]
  9. Time to Reach Maximum Concentration (Tmax) of Pexidartinib and its Primary Metabolite ZAAD-1006a [ Time Frame: Week 1, Week 3 at predose, 0.5h, 1h, 2h, 4h, and 6h postdose, Week 5, Week 9 and Week 17 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 × 109/L
    • Hemoglobin > 10 g/dL
    • Platelet count ≥ 100 × 109/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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04488822


Contacts
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Contact: Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111(M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp

Locations
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Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan
Contact: Principal Investigator         
Taipei Veterans General Hospital Recruiting
Taipei, Taiwan
Contact: Principal Investigator         
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
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Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT04488822    
Other Study ID Numbers: PL3397-A-A303
First Posted: July 28, 2020    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
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.
URL: https://vivli.org/ourmember/daiichi-sankyo/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Tenosynovial Giant Cell Tumor
Pexidartinib
TURALIO™
PLX3397
Additional relevant MeSH terms:
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Giant Cell Tumors
Giant Cell Tumor of Tendon Sheath
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Synovitis
Joint Diseases
Musculoskeletal Diseases
Tendinopathy
Muscular Diseases