1 / 31

SARC011/NO21157

SARC011/NO21157. Alberto Pappo, M.D. Texas Children’s Cancer Center Houston, TX. SARC011/NO21157.

robert
Télécharger la présentation

SARC011/NO21157

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. SARC011/NO21157 Alberto Pappo, M.D. Texas Children’s Cancer Center Houston, TX

  2. SARC011/NO21157 SARC Global Collaboration: A Phase II trial of R1507, a recombinant human monoclonal antibody to the insulin-like growth factor-1 receptor for the treatment of patients with recurrent or refractory Ewing’s sarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas 2 2

  3. Pt. 8012 Baseline Dec 8, 2006 Restaging Week 6 Jan 25, 2007 R1507 shows anti-tumor activity in the clinic- Phase I Pt. 7002 • Patient 7002: • 27yo male • Ewing’s sarcoma of chest wall with lung metastasis (1997) • SD → Partial Response after 25 weeks of R1507 at 1 mg/kg/week. Baseline June 19, 2006 Restaging Week 25 Dec 29, 2006 • Patient 8012: • 28yo female • Ewing’s sarcoma of sacrum with lung metastasis (2003) • PR after 6 weeks of R1507 at 9 mg/kg/week

  4. Determine the ORR to R1507 in pts with recurrent or refractory Ewing sarcoma (secondary cohort) osteosarcoma, synovial sarcoma, rhabdomyosarcoma, and other sarcomas: ASPS, CCS, EMS, DSRCT, MLS Determine PFS at 18 wks for patients treated with R1507 with progressive, recurrent or refractory ESFT (primary cohort) SARC011/NO21157 Primary Objectives

  5. SARC 011Secondary Objectives • Determine duration of response, PFS at 18 wks and overall PFS for pts with recurrent or refractory osteosarcoma, synovial sarcoma, rhabdomyosarcoma, and other sarcomas-ASPS, CCS, EMS,DSRCT, MLS. • Determine ORR, response duration, overall PFS in patients with Ewing sarcoma • PK,Tolerability and AE profile of R 1507

  6. PET scan changes Serum Biomarkers SARC011/NO21157 Exploratory Objectives

  7. Protocol Amendment v3 8-1-08 • Reduced the age from ≥ 12 to ≥ 2 years • Expanded “others” cohort to 10 patients for each subtype, then if 1PR an additional 10 patients • Alveolar Soft Part Sarcoma • Clear Cell Sarcoma • Extraskeletal Myxoid Chondrosarcoma • Desmoplastic Round Cell Tumor • Myxoid Liposarcoma

  8. SARC011/NO21157 Statistical Considerations • Ewing’s Primary cohort • Relapse ≤ 24 months AND at least 2 previous chemo regimen, surgically unresectable • 65 patients • Two stage design • Ewing’s Secondary cohort (all other Ewing’s patients) • Relapse > 24 months (or ≤ 24 months 1 chemo regimen) • 35 patients • Two stage design

  9. SARC011/NO21157Statistical Considerations • Osteosarcoma, Rhabdomyosarcoma, Synovial Sarcoma • 35 patients • Two stage design • Other Sarcomas • 20 patients for each of 5 other subtypes • Two stage design within each of the 5 subtypes

  10. WHO Criteria Bi-dimensional measurements Complete response (CR) Disappearance of all known disease Partial response (PR) ≥ 50% decrease Stable disease (SD) No 50% decrease & no 25% increase Progressive disease (PD) ≥ 25% increase

  11. Interim Analysis • Open to Recruitment: • Ewing’s 1 • Ewing’s 2 • Rhabdomyosarcoma • Other Sarcomas • Closed • Osteosarcoma • Undergoing interim analysis Synovial Sarcoma

  12. SARC011/NO21157Patient Enrollment • 28 centers are activated and open to enroll patients • n = 189 (177 eligible) • Age: • 12-86 yrs • Gender: (n=190*) • 118 Male • 72 Female *includes patient in screening data from Nov 1st, 2008

  13. Patient Enrollment-All Cohorts 189 enrolled 177 patients are eligible- data from Nov 1st, 2008

  14. Patient Enrollment-Ewing’s 68 eligible Ewing’s patients- data from Nov 1st, 2008

  15. Patient Enrollment by week All Patients Ewing’s Patients

  16. Patient Enrollment by month

  17. Ewing’s – Only 15% of Enrolled Patients < 18 data from Nov 1st, 2008

  18. SARC011/NO21157 Protocol Violations Patients must have measurable disease Index lesions must not be in prior site of radiation Index lesions must be ≥ 10mm by spiral CT or ≥ 20mm by conventional techniques Central pathology confirmation required within 6 weeks Dose of R1507 must not be adjusted unless there is a 10% change in weight

  19. Where do we need your help? • Ensuring patients are eligible • Enrolling pediatric patients • Enrolling Ewing’s 1 patients • Enrolling patients to the CBP • Sending samples for central path review • Sending pre study, baseline and efficacy scans to Bioimaging • Entering data answering queries

  20. SARC011/NO21157Enrollment by Cohort Nov 1, 2008

  21. SARC011/NO21157Enrollment by Others Cohort Nov 1, 2008 Clear Cell Sarcoma

  22. SARC011/NO21157Histologic Diagnosis (n=189) Nov 1, 2008 SS: synovial sarcoma OGS: osteosarcoma EWS-1: Ewing’s sarcoma primary EWS-2: Ewing’s sarcoma secondary MLS: myxoid liposarcoma EMC: extraskeletal myxoid chondrosarcoma DSRCT: desmoplastic small round cell tumor CCS: clear cell sarcoma ASPS: alveolar soft part sarcoma RMS: rhabdomyosarcoma

  23. SARC011/NO21157 SAEs Nov 1, 2008 *1 event of Thrombocytopenia, Adrenal Hemorrhage and Pulmonary embolism attributed to drug

  24. SARC011/NO21157 SAEs Nov 1, 2008

  25. Thank you

  26. Background slides

  27. SARC011/NO21157 Background The outcome for patients with recurrent sarcomas is uniformly poor Rhabdomyosarcoma n=605 Med age 8y [0-20y] Pappo et al. JCO, 17, 3487, 1999 27

  28. The outcome for patients with recurrent sarcomas is uniformly poor SARC011/NO21157 Background Ewing Sarcoma Jürgens ASCO 2007 Asbtract 10012 1 28

  29. SARC011/NO21157 Background The outcome for patients with recurrent sarcomas is uniformly poor Osteosarcoma n=575 Median age at Diagnosis 15.5 y [2.2 -68.2y] Kempf-Bielack et al. JCO, 23, 559, 2005 2 29

  30. 30

  31. SARC 011Background • R 1507 is a IGF-1 MoAb of the IgG1 subclass that binds the extracellular domain of IGF-1R and inhibits receptor activation • Main adverse events in about 40% of patients included GI, and fatigue but NO DLT • 4/59 HAHA (3 preexisting) • 9 mg/kg weekly. Half life 7 days • Responses: • 2/7 PR EWS • 5/19 SD

More Related