1 / 19

Phase II Study of Dasatinib in Advanced Sarcoma

Phase II Study of Dasatinib in Advanced Sarcoma. SARC 009 Coordinating site: University of Michigan. C-SRC expression in STS. Antibody AP7718a (Abgent) 1:50. C-SRC expression in STS. Tissue microarray – 181 samples. Dasatinib.

liesel
Download Presentation

Phase II Study of Dasatinib in Advanced Sarcoma

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Phase II Study of Dasatinib in Advanced Sarcoma SARC 009 Coordinating site: University of Michigan

  2. C-SRC expression in STS Antibody AP7718a (Abgent) 1:50

  3. C-SRC expression in STS Tissue microarray – 181 samples

  4. Dasatinib • Small molecule inhibitor of src-family kinases (src, bcr-abl) and PDGFR • Oral dosing • Short half-life • In vitro anti-tumor activity in rhabdomyosarcoma and osteosarcoma cell lines

  5. Sarcoma study objectives • Primary: Response rate • Secondary: • Progression-free survival rates • 2 and 5 year survival rates • Characterize Src expression • Collect tumor for molecular analysis if warranted

  6. Definition of Response CR PR CR PR CR PR SD SD SD PD PD PD Month 2 Month 4 Month 6

  7. Osteosarcoma Leiomyosarcoma Liposarcoma MFH MPNST Rhabdomyosarcoma High-grade chondrosarcoma ASPS Chordoma Epithelioid sarcoma GCT Hemangipericytoma Conventional chondrosarcoma Patient Strata Faster growth Slower growth

  8. PFS in phase II studies of previously treated soft tissue sarcoma

  9. Target activity: higher grade group • Target response rate at 6 months of at least 25% in “faster growth” group • Minimum 9 subjects accrued to each of 7 sub-groups

  10. PFS in phase II studies of “indolent” sarcomas

  11. Target activity: indolent group • Target response benefit rate at 6 months of at least 50% in “slower growth” group • Response rate < 25% will be considered unpromising • Minimum of 10 subjects accrued

  12. Patient eligibility • Group 1: Advanced leiomyosarcoma, MFH, liposarcoma, MPNST, rhabdomyosarcoma, osteosarcoma treated with 1 or more prior therapies • Group 2: ASPS, chondrosarcoma, chordoma, GCT, epithelioid sarcoma, hemangiopericytoma • Measurable disease • Age > 13 • Weight > 50 kg • ECOG score 0-2

  13. Exclusions • Acquired or congenital bleeding disorder • Taking anticoagulants or antiplatelet agents • On meds with risk of Torsades de Pointes • QTc interval >450 msec • LVEF <45% (measurement not required in all subjects) • Concurrent bisphosphonate therapy not allowed

  14. Treatment plan • Dasatinib 100mg twice daily Q 28 days • CBC weekly 1st month • Visits and labs monthly x 6 months, then q 6 weeks x 6 months then q 3 months • Tumor imaging every 2 months +/- 1 week x 6 months then q 3 months • Treat until progression or unmanageable toxicity

  15. Dose modification • Intolerable Grade 2 toxicity, reduce dose 1 level • Grade 3 or 4 toxicity, hold until < Grade 1, then restart at next lower dose

  16. Dasatinib AEs • Rash • GI disturbance, nausea, vomiting • Hypocalcemia • Fluid retention, pleural effusions • Hemorrhage • Cardiomyopathy

  17. Response assessment • Baseline chest imaging required • Imaging every 8 weeks • Choi criteria • > 10% increase in sum of greatest diameter of target lesions or new lesions = progression • > 10% decrease in sum of greatest diameter of target lesions = response • Neither 1 nor 2 = stable

  18. Logistics • Subjects registered through SARC • Local pathologist diagnoses sub-type • Dasatinib ordered by site from 3rd party supplier • Archival tumor tissue shipped to UM • Electronic data capture (Harvard server?)

  19. Implementation timeline • Protocol approved by BMS, supplying drug • Protocol approved by SARC • Submit to UM PRC/IRB in December • Distribute to SARC sites after approval

More Related