clinical trials for meningiomas andrew norden, m.d
TRANSCRIPT
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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
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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 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
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Hormonal Therapy:Somatostatin Analogs
Schulz et al. Clin Cancer Res 2000;6:1865-74.
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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
1Requires occasional assistance, but cares for most personal needs
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Targeted Molecular Therapies
Perry et al. J Neurooncol 2004;70:183-202
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Molecular Targets
Drappatz J, Wen PY. Expert Rev Neurother 2006;6:1465-79.
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TumorVEGF
Bevacizumab
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VEGFR Inhibitors
Blood vesselendothelial cell
VEGFR
Angiogenesis
X
DRUG
Phosphorylated receptor
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-treatmentPerfusion ratio = 7.4
Post-treatmentPerfusion 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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