Imatinib Mesylate and Hydroxyurea in Treating Patients With Recurrent or Progressive Meningioma

NCT00354913 | Completed Phase 2 Results DMC

• 3 other identifiers: Pro00006768DUMC-7082-05-4R0NOVARTIS-DUMC-7082-05-4R0
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as hydroxyurea, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib mesylate together with hydroxyurea may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving imatinib mesylate together with hydroxyurea works in treating patients with recurrent or progressive meningioma.

Conditions

Glioblastoma; Gliosarcoma

Keywords

adult grade I meningioma; adult grade II meningioma; adult grade III meningioma; adult papillary meningioma; adult anaplastic meningioma; recurrent adult brain tumor; glioblastoma multiforme (GBM); Imatinib; Imatinib mesylate; Hydroxyurea; Droxia; Hydrea; Hydroxycarbamide; Gleevec; Meningioma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival at 6 Months

  Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or death due to any cause.

  From the date of study treatment initiation to the date of the first documented progression or death from any cause, whichever came first, assessed up to 69 months. For each participant, PFS was assessed at 6 months after treatment initiation.

Secondary Outcomes (3)

• Median Progression-free Survival (PFS)

  From the date of study treatment initiation to the date of the first documented progression or death from any cause, whichever came first, assessed up to 69 months.

• Median Overall Survival (OS)

  From the date of study treatment initiation to the date of death from any cause, assessed up to 69 months.

• Objective Response Rate

  69 Months

Study Arms (1)

Imatinib mesylate+hydroxyurea

EXPERIMENTAL

All patients receive imatinib mesylate and hydroxyurea orally on a daily, continuous basis. Dosing of imatinib mesylate is adjusted for patients who are also receiving p450-inducing anti-epileptic drugs.

Drug: hydroxyurea; Drug: imatinib mesylate

Interventions

hydroxyurea DRUG

Hydroxyurea is administered orally twice a day. The dose will be set at 500 mg twice a day for all patients. If vomiting occurs not additional trial medication should be taken that day in an effort to replace the material that has been vomited. It is recommended that patients take their prescribed hydroxyurea at the same time that they take their prescribed imatinib mesylate, however, a 30-60 minute interval between agents is acceptable, if required for practical or other compliance issues.

Also known as: Droxia, Hydrea, Hydroxycarbamide

Imatinib mesylate+hydroxyurea

imatinib mesylate DRUG

Imatinib administered orally on daily, continuous basis. Imatinib doses of 400mg/600mg administered once daily, whereas daily doses of 800mg/greater administered as equally divided dose taken twice day. Dose for Imatinib: Patients receiving p450-inducing antiepileptic drugs:500mg twice day Patients not receiving p450-inducing antiepileptic drugs:400mg/day. If patients who were not on Cytochrome P450, family 3, subfamily A (CYP3A) enzyme-reducing anti-epileptic drug (EIAED) when originally enrolled must initiate CYP3A enzyme-inducing anti-epileptic drug while on study, study regimen will remain same for minimum of 2 wks before pt transitions to dosing as specified for patients on anti-epileptic drug. If patients originally enrolled must discontinue all EIAEDs while on study, in interest of patient safety, dosing of study regimen will transition to that of patients not on anti-epileptics immediately.

Also known as: Gleevec

Imatinib mesylate+hydroxyurea

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed meningioma * Recurrent or progressive disease after prior surgical resection * Measurable disease by contrast-enhanced MRI * Multifocal disease allowed * No evidence of intratumor hemorrhage on pretreatment diagnostic imaging * Stable postoperative grade 1 hemorrhage allowed * No peripheral edema or central or systemic fluid collections ≥ grade 2 (e.g., pericardial effusion, pulmonary effusion, ascites) PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Absolute neutrophil count \> 1,500/mm³ * Hemoglobin \> 9 g/dL * Platelet count \> 100,000/mm³ * Potassium normal\* * Calcium normal\* * Magnesium normal\* * Phosphorus normal\* * alanine aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN * Creatinine \< 1.5 times ULN OR creatinine clearance \> 50 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No excessive risk of bleeding, as defined by stroke within the past 6 months * No active systemic bleeding (i.e., gastrointestinal bleeding or gross hematuria) * No history of central nervous system (CNS) or intraocular bleeding or septic endocarditis * No concurrent severe and/or uncontrolled medical disease, including any of the following: * Uncontrolled diabetes * Congestive cardiac failure * Myocardial infarction within the past 6 months * Poorly controlled hypertension * History of labile hypertension * History of poor compliance with antihypertensive regimen * Chronic renal disease * Active uncontrolled infection requiring intravenous antibiotics * No acute or chronic liver disease (i.e., hepatitis, cirrhosis) * No HIV positivity * No impairment of gastrointestinal function or disease that may significantly alter the absorption of imatinib mesylate, including any of the following: * Ulcerative disease * Uncontrolled nausea * Vomiting * Diarrhea * Malabsorption syndrome * Bowel obstruction * Inability to swallow tablets * No other malignancy within the past 5 years except basal cell skin cancer or cervical carcinoma in situ NOTE: \*Unless correctable with supplements PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from prior therapy * More than 1 week since prior tumor biopsy * More than 2 weeks since prior surgical resection * Prior hydroxyurea allowed provided patient has not had progressive disease or toxicity \> grade 3 * No prior imatinib mesylate or other platelet-derived growth factor-directed therapy * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)\* * Chemotherapeutic agents such as etoposide that are normally given at shorter intervals allowed even if \< 4 weeks from last prior dose of chemotherapy * At least 4 weeks since prior radiotherapy\* * At least 1 week since prior biological, immunotherapeutic, or cytostatic drugs * At least 2 weeks since prior investigational drugs * No concurrent warfarin NOTE: \*Unless there is unequivocal evidence of tumor progression

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

Sponsors & Collaborators

• Duke University: lead
• National Cancer Institute (NCI): collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Reardon DA, Norden AD, Desjardins A, Vredenburgh JJ, Herndon JE 2nd, Coan A, Sampson JH, Gururangan S, Peters KB, McLendon RE, Norfleet JA, Lipp ES, Drappatz J, Wen PY, Friedman HS. Phase II study of Gleevec(R) plus hydroxyurea (HU) in adults with progressive or recurrent meningioma. J Neurooncol. 2012 Jan;106(2):409-15. doi: 10.1007/s11060-011-0687-1. Epub 2011 Sep 22.

  PMID: 21938530 RESULT

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Meningioma; Brain Neoplasms

Interventions

Hydroxyurea; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Benzamides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Dr. Annick Desjardins
• Organization: Duke University Medical Center

annick.desjardins@dm.duke.edu

919-681-1691

Study Officials

• David A. Reardon, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: July 19, 2006
• First Posted: July 20, 2006
• Study Start: May 1, 2005
• Primary Completion: March 1, 2009
• Study Completion: October 1, 2010
• Last Updated: January 18, 2013
• Results First Posted: January 14, 2013

Record last verified: 2012-12

Locations

US (1)