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

This study has been completed.
Sponsor:
Collaborators:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00354913
First received: July 19, 2006
Last updated: January 14, 2013
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Glioblastoma
Gliosarcoma
Drug: hydroxyurea
Drug: imatinib mesylate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Imatinib Mesylate Plus Hydroxyurea in the Treatment of Patients With Recurrent/Progressive Meningioma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Progression-free Survival at 6 Months [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Median Progression-free Survival (PFS) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.

  • Median Overall Survival (OS) [ Time Frame: From the date of study treatment initiation to the date of death from any cause, assessed up to 69 months. ] [ Designated as safety issue: No ]
    Time in months from the start of study treatment to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.

  • Objective Response Rate [ Time Frame: 69 Months ] [ Designated as safety issue: No ]
    Percentage of participants with an objective response (complete response or partial response). Per modified Macdonald criteria and assessed by MRI, complete response (CR) was the disappearance of all target lesions and partial response (PR) was a ≥50% decrease in the sum of the longest diameter of target lesions. Objective response = CR+PR.


Enrollment: 21
Study Start Date: May 2005
Study Completion Date: October 2010
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imatinib mesylate+hydroxyurea
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
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.
Other Names:
  • Droxia
  • Hydrea
  • Hydroxycarbamide
Drug: imatinib mesylate

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.

Other Name: Gleevec

Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the activity of imatinib mesylate and hydroxyurea, as measured by 6-month progression-free survival, in patients with recurrent or progressive meningioma.

Secondary

  • Evaluate the progression-free survival (PFS)
  • Overall survival (OS),
  • Objective response rate among patients treated with this regimen.

OUTLINE: This is an open-label study.

Patients receive oral imatinib mesylate once or twice daily and oral hydroxyurea twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00354913

Locations
United States, North Carolina
Duke Cancer Institute
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Novartis Pharmaceuticals
Investigators
Principal Investigator: David A. Reardon, MD Duke Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00354913     History of Changes
Obsolete Identifiers: NCT00611234
Other Study ID Numbers: Pro00006768, DUMC-7082-05-4R0, NOVARTIS-DUMC-7082-05-4R0
Study First Received: July 19, 2006
Results First Received: December 7, 2012
Last Updated: January 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
adult grade I meningioma
adult grade II meningioma
adult grade III meningioma
adult papillary meningioma
adult anaplastic meningioma
Meningioma
recurrent adult brain tumor
glioblastoma multiforme (GBM)
Imatinib
Imatinib mesylate
Hydroxyurea
Droxia
Hydrea
Hydroxycarbamide
Gleevec

Additional relevant MeSH terms:
Meningioma
Glioblastoma
Gliosarcoma
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
Imatinib
Hydroxyurea
Anticonvulsants
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Antisickling Agents
Hematologic Agents

ClinicalTrials.gov processed this record on October 19, 2014