1 / 12

Phase II Study of Dasatinib in Advanced Sarcomas SARC 009

Phase II Study of Dasatinib in Advanced Sarcomas SARC 009. Study PI: Scott Schuetze Registration and eCRF: CRAB Drug supply: BMS. Dasatinib. Small molecule inhibitor of src-family kinases (src, bcr-abl) and PDGFR Oral dosing Short half-life

lamont
Download Presentation

Phase II Study of Dasatinib in Advanced Sarcomas SARC 009

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 SarcomasSARC 009 Study PI: Scott Schuetze Registration and eCRF: CRAB Drug supply: BMS

  2. Dasatinib • Small molecule inhibitor of src-family kinases (src, bcr-abl) and PDGFR • Oral dosing • Short half-life • Toxicities: diarrhea, headache, hemorrhage, fatigue, nausea, rash, dyspnea, myelosuppression, hypocalcemia, hypophosphatemia, pleural effusion • Rare: prolongation QT, cardiomyopathy

  3. Dasatinib study objectives • Evaluate clinical benefit rate = objective response or lack of progression for 6 months • Evaluate 2 and 5 year survival rates • Assess clinical and laboratory toxicities • Collect tumor for construction of TMA • Collect blood samples for determionation of drug level and functional inhibition of SRC phosphorylation

  4. “aggressive” sarcoma sub-types • Osteosarcoma - 6 • Ewing’s family - 0 • Leiomyosarcoma - 9 • Liposarcoma - 8 • MFH - 4 • MPNST - 2 • Rhabdomyosarcoma - 2 N = min 9 – max 48 per stratum

  5. “Indolent” stratum • ASPS - 0 • Chordoma - 1 • Epithelioid sarcoma - 0 • GCT - 0 • Hemangiopericytoma - 3 • Conventional chondrosarcoma - 3 N = min 10 – max 116

  6. Patient eligibility • Measurable disease • Age > 13 years, weight > 50 kg • ECOG 0-2 • ANC > 1,500, Plt > 75,000 • Creatinine < 2x ULN • Serum calcium, magnesium and potassium > LLN • PT/PTT < 1.5x ULN • QTc interval < 450 msec • LVEF > 45%

  7. Exclusions/prohibitions • Disease curable by multidisciplinary management • Anti-platelet agents • Anticoagulants • Medications that prolong QT • Active cardiac disease within 6 months • Antacids – PPI, H-2 blockers • IV bisphosphonates • St John’s wort

  8. Treatment plan • Archival tissue to be submitted to UM (mandatory – all sites) • Negative pregnancy test prior to starting drug • CBC weekly 1st month, then monthly • Serum chemistries monthly • H&P monthly • ECG after 1st cycle • Serum sample pre and post dose 2-4 weeks after starting (selected sites) • Response assessment every 2 months +/- 1 week – on time reporting of response essential

  9. Dose adjustment • Dasatinib – NEW dosing scheme • 70 mg bid starting dose • 50 mg bid level -1 • 100 mg once daily level -2 • Intolerable grade 2 event, reduce dose without interruption • Clinically significant non-hematologic grade 3 event, hold dose until grade 1 and then restart at reduced dose • Grade 4 non-hematologic event, hold dose until grade 1 and then restart at reduced dose • Grade 3 or 4 neutropenia or thrombocytopenia, hold dose until grade 1 and then restart at reduced dose

  10. Correlative studies • Create sub-type specific TMAs – stored at UM, SARC sites will have access • Plasma sample obtained 2 hours after am dose 2 – 4 weeks after starting, store -20C or below – collection kits provided by SARC • PBMC lysate from sample pre and post am dasatinib dose 2 – 4 weeks after starting, store -70C or lower– collection kits provided by SARC

  11. SARC 009: Accrual 10/07 • UM – 20 • Penn (Staddon) – 8 • Washington Cancer I – 2 • Stanford – 3 • City of Hope – 3 • Kootenai ID - 1 • Oncology Specialists IL – open • Arkansas Childrens - open

  12. SARC 009: SAE 20 SAE – 12 related / 8 unrelated • Dyspnea – 6 • Pleural effusion – 2 • Pneumonia – 1 • Urinary tract infection - 1 • Nausea, vomiting, diarrhea – 3 • GI bleeding – 1 • Hyponatremia – 1 • Sudden cardiac arrest – 1 • Tumor related pain - 3

More Related