Tumour of the tendon sheath
Conditions
Interventions
Subjects will take five capsules a day (1000 mg/d Pexidartinib or matching
placebo) divided into a morning dose of two capsules and an evening dose of
three capsules for the first 2 weeks in Part 1.
Giant Cell Tumor
Pigmented Villonodular Synovitis
Tendon Sheath
Sponsors
Daiichi Sankyo, Inc
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
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 as defined by RECIST 1.1 (except that a minimal size of 2cm is required) , 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: a. 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"). b. 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 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 (e.g., condom, diaphragm) used in combination with hormonal methods associated with inhibition of ovulation. Women of nonchild bearing 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 an FSH level > 40 mIU/mL will be considered postmenopausal. 9. Adequate hematologic, hepatic, and renal function, defined by: * Absolute neutrophil count * 1.5× 109 /L * AST/ALT * 1.5× 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 BPI 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 a 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
Exclusion criteria: 1. Investigational drug use within 28 days of randomization. 2. 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, 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, or carcinoma insitu of the cervix or breast or prostrate carcinoma with a prostate specific antigen value
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Mean change from baseline in range of motion of the affected joint, relative to a reference standard for the same joint, at the Week 25 visit 2. Proportion of responders based on centrally evaluated MRI scans and TVS at the Week 25 visit 3. Mean change from baseline score in the PROMIS Physical Function Scale at the Week 25 visit 4. Mean change from baseline score in the Worst Stiffness NRS item at the Week 25 visit 5. Protoption of responders based on the BPI Worst Pain NRS item and analgesic use by BPI-30 definition 6. Duration of response (CR or PR) based on MRI and RECIST 1.1 7. Duration of response (CR or PR) based on MRI and TVS | — |
Countries
Australia, Canada, Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, United Kingdom, United States of America
Outcome results
None listed