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Combination of Hydroxyurea and Verapamil for Refractory Meningiomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00706810
Recruitment Status : Completed
First Posted : June 30, 2008
Results First Posted : April 13, 2017
Last Update Posted : April 13, 2017
Information provided by (Responsible Party):
University of Utah

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).

Condition or disease Intervention/treatment Phase
Cancer Brain Cancer Meningioma Drug: Hydroxyurea Drug: Verapamil Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
Official Title: Combination of Hydroxyurea and Verapamil for Refractory Meningiomas
Study Start Date : December 2007
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Hydroxyurea

Arm Intervention/treatment
Experimental: All participants Drug: Hydroxyurea
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.

Drug: Verapamil
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.

Primary Outcome Measures :
  1. Number of Participants Experiencing Serious Adverse Events Including But Not Limited to Hospitalizations, Deaths Related to Treatment, or Other Incapacitating Conditions. [ Time Frame: two years ]
    Adverse Events assessed in accordance with CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0.

Secondary Outcome Measures :
  1. Median Progression-free Survival Rates of the Treatment Population. [ Time Frame: 31 months ]
    Response and progression will be evaluated in this study using measurements from the MRI/CT scans. Measurements will be made of the image slice with the largest cross sectional area. Two orthogonal measures will be made to determine maximal AP and lateral dimensions. Progression of disease will be defined as a greater than 25% increase of largest cross sectional area by two orthogonal measurements, taking as reference the smallest sum recorded since the treatment started or the appearance of one or more new lesions.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  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

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00706810

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United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
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Principal Investigator: Randy Jensen, MD, Ph.D. Huntsman Cancer Institute
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University of Utah Identifier: NCT00706810    
Other Study ID Numbers: HCI25089
First Posted: June 30, 2008    Key Record Dates
Results First Posted: April 13, 2017
Last Update Posted: April 13, 2017
Last Verified: March 2017
Keywords provided by University of Utah:
Brain cancer
Additional relevant MeSH terms:
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Brain Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Brain Diseases
Central Nervous System Diseases
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Anti-Arrhythmia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents