Clinical trial NCT00354913: Imatinib Mesylate and Hydroxyurea in Treating Patients With Recurrent or Progressive Meningioma
Official title: A Phase II Study of Imatinib Mesylate Plus Hydroxyurea in the Treatment of Patients With Recurrent/Progressive Meningioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Novartis Pharmaceuticals
First posted: 2006-07-20
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Progression-free Survival at 6 Months
timeFrame: 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:
measure: Median Progression-free Survival (PFS)
timeFrame: 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.
measure: Median Overall Survival (OS)
timeFrame: From the date of study treatment initiation to the date of death from any cause, assessed up to 69 months.
measure: Objective Response Rate
timeFrame: 69 Months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
Study officials:
affiliation: Duke Cancer Institute
name: David A. Reardon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.