Clinical Trials for Meningiomas

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Clinical Trials for Meningiomas

• Andrew Norden, M.D.
• Division of Cancer Neurology, Department of
  Neurology
• Brigham and Womens Hospital
• Center For Neuro-Oncology
• Dana-Farber Cancer Institute

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The Role of a Neuro-Oncologist

• Monitor the tumor for growth
• Evaluate and treat any symptoms
• Refer for surgery or radiation oncology
  consultation
• Prescribe chemotherapy
• Enroll in clinical trials

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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

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Cytotoxic Chemotherapy

• Adriamycin and dacarbazine
• Cyclophosphamide, adriamycin, and vincristine
  (CAV)
• Hydroxyurea
• Ifosfamide
• Interferon-alpha
• Irinotecan
• Temozolomide

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Hormonal TherapyProgesterone 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 200131510-3
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Hormonal TherapySomatostatin Analogs
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Octreotide Scans
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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

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Pasireotide (SOM230)

• More potent than octreotide
• Acts on a wider range of somatostatin receptors
  (especially sst1, 3, 5)
• Ongoing trial

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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

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Targeted Molecular Therapies
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Molecular Targets
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Tumor
VEGF
Bevacizumab
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VEGFR Inhibitors

• Examples
• Sunitinib
• Sorafenib
• Cediranib

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Angiogenesis and Meningiomas
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Peri-Tumoral Edema
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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

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Dynamic Contrast-Enhanced MRI
Pre-treatment Perfusion ratio 7.4
Post-treatment Perfusion ratio 3.9
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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

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