Combination of Hydroxyurea and Verapamil for Refractory Meningiomas

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT00706810
First received: June 26, 2008
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Cancer
Brain Cancer
Meningioma
Drug: Hydroxyurea
Drug: Verapamil
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination of Hydroxyurea and Verapamil for Refractory Meningiomas

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • To determine the safety of the combination of hydroxyurea and verapamil for treatment of patients with progressive, recurrent meningiomas. To characterize the toxicity of this drug combination. [ Time Frame: December 2011 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the objective response rate of patients treated with this drug combination by magnetic resonance imaging and metabolic PET imaging. • To determine the 12 month and 24 month progression-free survival rates of the treatment population [ Time Frame: December 2011 ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: December 2007
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00706810

Locations
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Randy Jensen, MD, Ph.D. Huntsman Cancer Institute
  More Information

No publications provided

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT00706810     History of Changes
Other Study ID Numbers: HCI25089
Study First Received: June 26, 2008
Last Updated: July 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
Cancer
Brain cancer
Meningioma

Additional relevant MeSH terms:
Meningioma
Brain Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Brain Diseases
Central Nervous System Diseases
Verapamil
Hydroxyurea
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Antineoplastic Agents
Antisickling Agents
Hematologic Agents
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014