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INTERGROUP COALITION AGAINST SARCOMAS (ICAS)

INTERGROUP COALITION AGAINST SARCOMAS (ICAS). A COMMITTEE FOCUSED ON INTERGROUP DEVELOPMENT OF NEW SARCOMA THERAPEUTICS CALGB ECOG NCIC SWOG Collaborations with COG and ACOSOG Communication with SARC and RTOG.

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INTERGROUP COALITION AGAINST SARCOMAS (ICAS)

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  1. INTERGROUP COALITION AGAINST SARCOMAS (ICAS) A COMMITTEE FOCUSED ON INTERGROUP DEVELOPMENT OF NEW SARCOMA THERAPEUTICS CALGB ECOG NCIC SWOG Collaborations with COG and ACOSOG Communication with SARC and RTOG • SCIENTIFIC STEERING COMMITTEE: EC Borden, G Demetri, M von Mehren, K Albritton, P Pisters • BIOSTATISTICS: C Rankin, J Crowley • OPERATIONS: G Goetz (SWOG)

  2. 2001-2006INTERGROUP COALITION AGAINST SARCOMAS Goals and Hypotheses • Sharpen definition of histologic subtypes to improve therapeutic outcomes and prognosis • Hypothesis: Molecular pathology will better define subtypes and thus improve clinical management and outcomes • Emphasize targeted therapeutics • Hypothesis: Signal transduction modulators will be effective and histology specific • Facilitate intergroup collaborations • Hypothesis: Increased intergroup collaboration will stimulate sarcoma research State of Science Clin Cancer Research 2003

  3. ICAS STUDIESMetastatic Disease: Completed ICAS #SarcomaTargetInhibitorPrior Rx S0033 GIST KIT imatinib Y S0218 Mesothelioma EGF-R erlotinib N S0330 MPNST EGF-R erlotinib N

  4. OVERALL SURVIVAL GIST ON IMATINIB (ICAS S0033) 100% 2y=74% 2y(historical)=26% 80% 60% 40% N Deaths MEDIAN (m) 400 mg/day 345 168 55 CR=4% PR=48% 800 mg/day 345 174 51 20% 0% 0 2 4 6 Years after Registration

  5. S0502: SCHEMA RANDOMIZE Imatinib mesylate 400 mg/d po continuously Bevacizumab 15 mg/kg iv q3 weeks Stratify PS 0-1 vs. 2-3 Incurable GIST Imatinib mesylate 400 mg/d po continuously

  6. S0502: Objectives • Primary:PFS of imatinib + bevacizumab vs imatinib alone • Secondary: • Compare response between arms • Compare frequency and severity of toxicities • Assess survival differences • Correlative • Mutations VEGF and Receptors • PET PK

  7. Study Coordinators • OVERALL CHAIR: Charles Blanke SWOG • Translational Medicine: Michael Heinrich SWOG • Pathology: Christopher Corless SWOG • ECOG: Meg von Mehren • CALGB: George Demetri • NCIC: Vivien Bramwell • Imaging: Janet Eary

  8. CTSU!!!!!! ICAS STUDIESMetastatic Disease: Active ICAS #SarcomaTargetInhibitorPrior Rx Accrual S0345 DFSP PDGF-R imatinib Y 7 S0346 Synovial HER2* trastuzumab Y 0 S0505 STS VEGF sorafenib Y 22 S0423 Chondro MTAP pemetrexed Y 11 S0344 Chondro ---- Surgery N 16

  9. CTSU!!!!! ICAS STUDIESMetastatic Disease: Planned ICAS #SarcomaTargetInhibitorPrior RxPI 0405 synovial (neoaj) bcl-2 antisense+AI N Albritton 0502 GIST c-kit VEGF Imatbbevamab N Blanke 0612 GIST KIT GW786034 Y Budd 0418 GIST <30y KIT imatinib N Pappo 0631 MFH/Osteo SRC dasatinib Y Chu

  10. ICAS STUDIESMetastatic Disease: Proposals for Executive Committee SarcomaTargetInhibitorPrior RxPI Desmoid PDGF-R sunitinib Y Ryan STS VEGF bevacizumab N* Verschraegen * Phase III: AI MFH m-TOR temsirolimus Y TBD

  11. CHALLENGES SARCOMAS: 2006 • CLINICAL BIOLOGY AND OUTCOMES • CURRENT MANAGEMENT AND STANDARDS OF CARE • EMPHASIZE CLINICAL PROGRESS

  12. CHALLENGES SARCOMAS: 2006 • CLINICAL BIOLOGY AND OUTCOMES • What do we know? • CURRENT MANAGEMENT AND STANDARDS OF CARE • How are we doing? • FUTURE RESEARCH CHALLENGES • Where should we be going?

  13. CHALLENGES SARCOMAS: 2006

  14. Euramos 1 Phase 3 TrialEuropean and American Osteosarcoma Study Group • Collaborators: COG German Austrian Swiss (COSS) European (EOI) Scandinavian (SSG) Trial Mgmt Group Chair M Bernstein Montreal COG • Objectives: Improve EFS • Will IE when added to MAP for poor histological responders? • Will PEG-IFN when added to MAP for good histological responders? • Eligibility • Resectable axial or extremity osteosarcoma • <40 • Registration2 cycles MAPsurgery path reveiw  Random MAPx2 MAPx2 MPx2PEG-IFNx2y or IEx3 • n=1400 • 10% improvement in EFS

  15. INTERGROUP COALITION AGAINST SARCOMAS (ICAS) Ernest C. Borden Chair • Catherine Rankin Biostatistics SWOG • John Crowley Biostatistics SWOG • Gretchen Goetz Operations SWOG • SWOG ECOG CALGB NCIC • collaboration with COG ACOSOG • M von Mehren G Demetri B Redman V Bramwell • K Albritton P Pisters • Communication with SARC A COMMITTEE FOCUSED ON INTERGROUP DEVELOPMENT OF NEW SARCOMA THERAPEUTICS

  16. SARCOMAS NEW ERA 2000 MOLECULAR REDEFINITION IMPROVE PRIMARY TREATMENT TARGETED THERAPIES

  17. IMPROVING GIST PATIENT OUTCOMES • Eliminating GIST stem cell • Few residual clones: ACOSOG #Z9001 • Imatinib with other KIT/PDGF-R tyrosine kinase inhibitors • S0612 • Targeting of specific mutations • S0033 • S0033 and EORTC combined analysis • new inhibitors: S0612 • Inhibition of alternate pathways • Angiogenesis: Bevacizumab S0502 • Improved resonse assessement • S0502

  18. ICASHER2 Expression in Synovial Sarcomas Her2/neu

  19. S0346 Trastuzumab for Synovial Sarcomas • Eligibility • Metastatic Synovial Sarcomas • Central confirmation of her2 expression 2+ • 1 prior treatment • Dose/Schedule • IV weekly 4 mg/kg loading, then 2 mg/kg

  20. SARCOMAS NEW ERA 2000 MOLECULAR REDEFINITION IMPROVED PRIMARY OUTCOMES TARGETED THERAPIES Case Comprehensive Cancer Center CCF Taussig Cancer Center

  21. IMPACT OF DOSE OF IMATINIB ON TOXICITY: ICAS S0033

  22. EGF-R EXPRESSION ANDINHIBITION IN MPNST Intense membrane staining EGF-R inhibitors DeClue et al JCI 2000

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