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Clinical Trials for Meningiomas Andrew Norden, M.D.
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Clinical Trials for Meningiomas Andrew Norden, M.D.

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  • Suprasellar meningioma mgh 4434036
  • NF2
  • Recurrent malignant meningioma
  • 21303227
  • Transcript

    • 1. Clinical Trials for MeningiomasClinical Trials for Meningiomas Andrew Norden, M.D. Division of Cancer Neurology, Department of Neurology Brigham and Women’s Hospital Center For Neuro-Oncology Dana-Farber Cancer Institute
    • 2. When to Consider Clinical Trials • Surgery or radiation cannot be given safely • The tumor begins to grow after maximal surgery and radiation • You and your treatment team think that clinical trials may be appropriate
    • 3. Cytotoxic Chemotherapy • Adriamycin and dacarbazine • Cyclophosphamide, adriamycin, and vincristine (CAV) • Hydroxyurea • Ifosfamide • Interferon-alpha • Irinotecan • Temozolomide
    • 4. Hormonal Therapy: Progesterone Receptor Blockers • Phase III Trial - Grunberg et al (ASCO 2001): – Unresectable benign and atypical meningiomas (193 patients) – Randomized to RU-486 200 mg daily or placebo – Well tolerated: common toxicities were fatigue, headache, and hot flashes – No benefit from RU-486 Kubo et al. Jpn J Clin Oncol 2001;31:510-3
    • 5. Hormonal Therapy: Somatostatin Analogs Schulz et al. Clin Cancer Res 2000;6:1865-74.
    • 6. Octreotide Scans
    • 7. Depot Octreotide Acetate (Sandostatin LAR) • Chamberlain et al (Neurology 2007) – 16 patients (8 benign, 3 atypical, 5 malignant) – Positive octreotide scans – Sandostatin LAR 20-40 mg IM monthly – Few side effects – After 3 months, 31% partial responses and 31% stable tumors – 44% six-month progression-free survival
    • 8. Pasireotide (SOM230) • More potent than octreotide • Acts on a wider range of somatostatin receptors (especially sst1, 3, 5) • Ongoing trial
    • 9. Phase 2 SOM230 LAR Trial • Dosing: 60 mg IM every 28 days • Eligibility criteria: recurrent or inoperable meningioma, KPS 601 , no limit to prior therapy • Very well tolerated • 6/40 patients enrolled • Sites: DF/HCC, Memorial Sloan-Kettering, Wake-Forest, Duke, Northwestern, Univ. of Washington, Cedars-Sinai 1 Requires occasional assistance, but cares for most personal needs
    • 10. Targeted Molecular Therapies Perry et al. J Neurooncol 2004;70:183-202
    • 11. Molecular Targets Drappatz J, Wen PY. Expert Rev Neurother 2006;6:1465-79.
    • 12. Tumor VEGF Bevacizumab
    • 13. VEGFR Inhibitors Blood vessel endothelial cell VEGFR Angiogenesis X DRUG Phosphorylated receptor Examples • Sunitinib • Sorafenib • Cediranib
    • 14. Angiogenesis and Meningiomas
    • 15. Peri-Tumoral Edema
    • 16. Phase 2 Sunitinib Trial • Dosing: 50 mg daily for 4 weeks, 2 weeks off • Eligibility criteria: recurrent or inoperable meningioma, KPS 60, no limit to prior therapy • Side effects: fatigue, rash, diarrhea • Sites: DF/HCC, Memorial Sloan-Kettering, UVA • Results in first 10 patients (Kaley et al., SNO 2008): 1 partial response, 8 stable tumors, 50% six-month progression-free survival rate
    • 17. Dynamic Contrast-Enhanced MRI Pre-treatment Perfusion ratio = 7.4 Post-treatment Perfusion ratio = 3.9
    • 18. Summary and Conclusions • Clinical trial options may be considered if surgery and radiation are unsafe or ineffective • Promising approaches include: – Somatostatin analogs – Targeted molecular drugs in various combination – Anti-angiogenic agents • Advances in meningioma biology will continue to drive progress in therapeutics