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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)

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ClinicalTrials.gov Identifier: NCT02371369
Recruitment Status : Active, not recruiting
First Posted : February 25, 2015
Last Update Posted : January 23, 2019
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE February 19, 2015
First Posted Date  ICMJE February 25, 2015
Last Update Posted Date January 23, 2019
Actual Study Start Date  ICMJE March 2015
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 13, 2018)
  • Percentage of participants achieving complete or partial response at Week 25 [ Time Frame: at Week 25 ]
    The percentage of participants who achieved a complete response (CR) or partial response (PR) at the Week 25 visit based on centrally read MRI scans and RECIST 1.1.
  • Percentage of participants achieving complete or partial response by the end of the trial [ Time Frame: by the end of the trial, estimated at 46 months ]
    The percentage of participants who achieved a complete response (CR) or partial response (PR) by the end of the trial based on centrally read MRI scans and RECIST 1.1.
Original Primary Outcome Measures  ICMJE
 (submitted: February 19, 2015)
percentage of subjects achieving complete or partial response [ Time Frame: week 25 ]
The proportion of subjects who achieve a complete response (CR) or partial response (PR) at the Week 25 visit based on centrally read MRI scans and RECIST 1.1.
Change History Complete list of historical versions of study NCT02371369 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2018)
  • Patient Reported Outcome (PRO): Physical Function [ Time Frame: to the end of the trial, estimated to be at 46 months ]
    Participants rate their physical function using the standard Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale
  • PRO: Worst Pain [ Time Frame: to the end of the trial, estimated to be at 46 months ]
    Participants rate their pain on a numerical rating scale (NRS) from 0-10, where 0="no pain" and 10="pain as bad as you can imagine".
  • PRO: Worst Stiffness [ Time Frame: to the end of the trial, estimated to be at 46 months ]
    Participants rate their stiffness on a NRS from 0-10, where 0="no stiffness" and 10="stiffness as bad as you can imagine"
  • Percentage of participants achieving complete or partial response based on Tumor Volume Score [ Time Frame: to the end of the trial, estimated to be at 46 months ]
    The percentage of participants who achieved a CR or PR based on tumor volume score
  • Mean range of motion [ Time Frame: to the end of the trial, estimated to be at 46 months ]
  • Duration of response [ Time Frame: to the end of the trial, estimated to be at 46 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2015)
  • composite of patient reported outcomes [ Time Frame: week 25 ]
    evaluate composite patient-reported outcomes (PROs), including the Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) item, Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale, and Worst Stiffness NRS item, at Week 25;
  • response based on Tumor Volume Score [ Time Frame: week 25 ]
    Response based on Tumor Volume Score (TVS)
  • range of motion [ Time Frame: week 25 ]
  • duration of response. [ Time Frame: week 25 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Study of Pexidartinib for Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS)
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Parallel assignment in Part 1, Single treatment in Part 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) in Part 1, Open-label (no masking) in Part 2
Primary Purpose: Treatment
Condition  ICMJE
  • Pigmented Villonodular Synovitis
  • Giant Cell Tumors of the Tendon Sheath
  • Tenosynovial Giant Cell Tumor
Intervention  ICMJE
  • Drug: Pexidartinib
    Each capsule contains 200 mg of pexidartinib for oral administration
    Other Names:
    • PLX3397
    • Pexidartinib hydrochloride (HCl)
  • Drug: Placebo
    Placebo capsule matching pexidartinib capsule for oral administration
    Other Name: Placebo Capsule
Study Arms  ICMJE
  • Experimental: Part 1 - 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
    Intervention: Drug: Pexidartinib
  • Placebo Comparator: Part 1 - 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
    Intervention: Drug: Placebo
  • Experimental: Part 2 - All Pexidartinib
    Participants received pexidartinib in Part 1 and in Part 2 at their prescribed dose
    Intervention: Drug: Pexidartinib
  • Experimental: Part 2 - Placebo-Pexidartinib
    Participants received placebo in Part 1 and pexidartinib in Part 2 at their prescribed dose
    Interventions:
    • Drug: Pexidartinib
    • Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 13, 2017)
120
Original Estimated Enrollment  ICMJE
 (submitted: February 19, 2015)
126
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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 (nonhormonal 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 × 109/L
    • aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤ 1.5 × upper limit of normal (ULN)
    • Hemoglobin > 10 g/dL
    • Total bilirubin ≤ 1.5 × ULN
    • Platelet count ≥ 100 × 109/L
    • Serum creatinine ≤ 1.5 × ULN
  10. Willingness and ability to complete the Worst Pain NRS item, Worst Stiffness NRS item, 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Denmark,   France,   Germany,   Hungary,   Italy,   Netherlands,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02371369
Other Study ID Numbers  ICMJE PLX108-10
2014-000148-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
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/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Team Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP