Combination of Hydroxyurea and Verapamil for Refractory Meningiomas

NCT00706810 | Completed Phase 2 Results DMC

• 1 other identifier: HCI25089
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Cancer; Brain Cancer; Meningioma

Keywords

Cancer; Brain cancer; Meningioma

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Serious Adverse Events Including But Not Limited to Hospitalizations, Deaths Related to Treatment, or Other Incapacitating Conditions.

  Adverse Events assessed in accordance with CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0.

  two years

Secondary Outcomes (1)

• Median Progression-free Survival Rates of the Treatment Population.

  31 months

Study Arms (1)

All participants

EXPERIMENTAL

Drug: Hydroxyurea; Drug: Verapamil

Interventions

Hydroxyurea DRUG

Hydroxyurea inhibits DNA synthesis by inhibition of ribonucleotide diphosphate reductase and is a well-known drug used for the treatment of a number of tumor types including head and neck tumors and chronic myelogenous leukemia. It has also been used as an adjuvant for antiretroviral treatment for patients with HIV and as a treatment for polycythemia vera, essential thrombocythemia and sickle cell disease.

All participants

Verapamil DRUG

Verapamil is another commonly used medication. It is used for the treatment of angina, hypertension, supraventricular arrhythmias, and migraine prophylaxis. Dosing with standard verapamil is 80-120 mg pox three times a day but the sustained release form can be given 120-480mg once or twice each day.

All participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Karsy M, Hoang N, Barth T, Burt L, Dunson W, Gillespie DL, Jensen RL. Combined Hydroxyurea and Verapamil in the Clinical Treatment of Refractory Meningioma: Human and Orthotopic Xenograft Studies. World Neurosurg. 2016 Feb;86:210-9. doi: 10.1016/j.wneu.2015.09.060. Epub 2015 Sep 30.

  PMID: 26428319 DERIVED

MeSH Terms

Conditions

Neoplasms; Brain Neoplasms; Meningioma

Interventions

Hydroxyurea; Verapamil

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms, Vascular Tissue; Meningeal Neoplasms

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Phenethylamines; Ethylamines; Amines

Results Point of Contact

• Title: Dr. Randy Jensen
• Organization: Huntsman Cancer Institute

randy.jensen@hci.utah.edu

801-581-6908

Study Officials

• Randy Jensen, MD, Ph.D.

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2008
• First Posted: June 30, 2008
• Study Start: December 1, 2007
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: April 13, 2017
• Results First Posted: April 13, 2017

Record last verified: 2017-03

Locations

US (1)