Clinical Trials for Meningiomas Andrew Norden, M.D.

851 views

Published on

  • Be the first to comment

Clinical Trials for Meningiomas Andrew Norden, M.D.

  1. 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. 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. 3. Cytotoxic Chemotherapy • Adriamycin and dacarbazine • Cyclophosphamide, adriamycin, and vincristine (CAV) • Hydroxyurea • Ifosfamide • Interferon-alpha • Irinotecan • Temozolomide
  4. 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. 5. Hormonal Therapy: Somatostatin Analogs Schulz et al. Clin Cancer Res 2000;6:1865-74.
  6. 6. Octreotide Scans
  7. 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. 8. Pasireotide (SOM230) • More potent than octreotide • Acts on a wider range of somatostatin receptors (especially sst1, 3, 5) • Ongoing trial
  9. 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. 10. Targeted Molecular Therapies Perry et al. J Neurooncol 2004;70:183-202
  11. 11. Molecular Targets Drappatz J, Wen PY. Expert Rev Neurother 2006;6:1465-79.
  12. 12. Tumor VEGF Bevacizumab
  13. 13. VEGFR Inhibitors Blood vessel endothelial cell VEGFR Angiogenesis X DRUG Phosphorylated receptor Examples • Sunitinib • Sorafenib • Cediranib
  14. 14. Angiogenesis and Meningiomas
  15. 15. Peri-Tumoral Edema
  16. 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. 17. Dynamic Contrast-Enhanced MRI Pre-treatment Perfusion ratio = 7.4 Post-treatment Perfusion ratio = 3.9
  18. 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

×