Combination of Hydroxyurea and Verapamil for Refractory Meningiomas

• Status: Completed
• Trial end date: 2015-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Meningiomas account for 20% of primary adult brain tumors, occurring at an annual incidence of 6 per 100,000 (Louis, Scheithauer et al. 2000). Complete surgical resection is the treatment of choice but may not possible when the tumor invades critical structures (e.g., skull base, sagittal sinus) (Mirimanoff, Dosoretz et al. 1985; al-Rodhan and Laws 1990; Al-Rodhan and Laws 1991; Newman 1994; De Monte 1995; Levine, Buchanan et al. 1999; Barnett, Suh et al. 2000; Ragel and Jensen 2003). Up to 20% of meningiomas exhibit a more aggressive phenotype that does not respond to standard therapies (Kyritsis 1996). Adjuvant therapies are critical for patients with this subset of meningiomas. Radiation therapy and stereotactic radiosurgery are good adjuvant therapies but are limited by radiation neurotoxicity, tumor size constraints, and injury to adjacent vascular structures or cranial nerves (Goldsmith, Wara et al. 1994; Barnett, Suh et al. 2000; Goldsmith and Larson 2000). Standard chemotherapeutic treatments have been disappointing (Kyritsis 1996). Even drugs like temozolomide that have shown efficacy against malignant brain tumors have failed to inhibit the growth of refractory meningiomas in a phase II study (Chamberlain, Tsao-Wei et al. 2004).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Utah
• Treatments: Hydroxyurea; Verapamil

Criteria

1. Must be age > 18 years

2. Patient able to provide written informed consent

3. Histologically confirmed meningioma of any WHO grade (written pathology report from surgery required)

4. Radiographic demonstration of at least 25% increase in tumor cross sectional area measured on CT/MRI within last 6 months

5. Patients refusing or for which there is no further surgical or radiation therapy options

6. WBC at least 2,500/mm3

7. Platelet count of at least 100,000/mm3

8. Hemoglobin > 8.0 g/dL

9. Renal insufficiency (glomerular filtration rate (GFR) < 60 as estimated by the Cockcroft-Gault equation) are ineligible

10. Hepatic disease (ALT, AST, bilirubin, or alkaline phosphatase > 3 times upper limit of normal) or known cirrhosis are ineligible

11. Clinically significant cardiovascular disease specifically those patients with the following conditions are ineligible:

• congestive heart failure

• known bundle branch or AV conduction problems

• 2nd or 3rd degree atrioventricular block (except in patients with artificial pacemaker),

• sick sinus syndrome

• atrial flutter or atrial fibrillation with an accessory bypass tract (Wolff-Parkinson-White Syndrome, Lown-Ganong-Levine Syndrome),

• history of myocardial infarction in the past 6 months

• currently taking beta-blockers, digoxin, or neuromuscular blocking agents

• Bradycardia (resting heart rate < 60 beats per minute)

12. Hypotension (resting blood pressure < 90 systolic)

13. Altered neuromuscular transmission (Duchenne Muscular Dystrophy, myasthenia gravis)

14. Karnofsky performance score 50-100%

15. Life expectancy more than 6 months

16. Pregnant or nursing females are ineligible. Fertile patients must use an effective contraception

17. Received prior investigational agents in the past 6 months are ineligible