Clinical trial NCT00904735: Hydroxyurea With or Without Imatinib Mesylate in Treating Patients With Recurrent or Progressive Meningioma
Official title: IMATINIB Plus Hydroxyurea in the Treatment of Recurrent or Progressive Meningiomas: a Randomized Phase II Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult grade I meningioma
adult grade II meningioma
adult anaplastic meningioma
adult papillary meningioma
recurrent adult brain tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-05-20
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: 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. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether hydroxyurea is more effective when given alone or together with imatinib mesylate in treating patients with meningioma.

PURPOSE: This randomized phase II trial is studying how well hydroxyurea works compared with giving hydroxyurea together with imatinib mesylate in treating patients with recurrent or progressive meningioma.

Detailed description: OBJECTIVES:

Primary

* Assess the progression-free survival of patients with recurrent or progressive meningiomas treated with hydroxyurea with vs without imatinib mesylate after surgery and radiotherapy.

Secondary

* Determine the overall survival, and response rate of patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to WHO grade (I vs II-III). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral hydroxyurea twice daily and oral imatinib mesylate once daily in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive oral hydroxyurea twice daily in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed for up to 1 year.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosed with meningioma

  * WHO grade I-III
* Recurrent or progressive disease after prior surgery and radiotherapy, or radiosurgery
* Not amenable to further surgery
* No optic nerve sheet tumor and neurofibromatosis type II
* No known brain metastasis

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* ANC \> 1,500/mm\^3
* Platelet count \> 100,000/mm\^3
* Hemoglobin ≥ 9 mg/dL (transfusion allowed)
* Total bilirubin \< 1.5 times upper limit of normal (ULN)
* SGOT and SGPT \< 2.5 times ULN
* Creatinine \< 1.5 times ULN
* Negative pregnancy test
* Fertile patients must use effective barrier method contraception during and for up to 3 months after completion of study therapy
* No second malignancy
* No known chronic liver disease (i.e., active hepatitis, cirrhosis)
* No known HIV infection
* No significant history of non-compliance to medical regimens or inability to grant reliable informed consent

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No concurrent enzyme-inducing anti-epileptic drugs
* No concurrent therapeutic anticoagulation with warfarin (e.g., Coumadin®)

  * Low-molecular weight heparin (e.g., Lovenox) or heparin allowed
  * Mini-dose Coumadin® (e.g., 1 mg QD) allowed for prophylaxis of central venous catheter thrombosis, at the discretion of the treating physician
* No concurrent acetaminophen (Efferalgan®, Tachipirina®) allowed during imatinib mesylate administration
* No other concurrent anticancer agents, including chemotherapy or biological agents
* No other concurrent investigational drugs

Primary outcomes:
measure: Progression-free survival, defined as ≥ 25% increase in tumor volume or new tumor on MRI
Secondary outcomes:
measure: Survival
measure: Response rate according to MacDonald criteria
measure: Toxicity as assessed by NCI CTCAE v. 3.0
Other outcomes:
Locations:
city: Avellino
country: Italy
facility: Ospedale Civile Avellino
city: Bologna
country: Italy
facility: Ospedale Bellaria
city: Florence
country: Italy
facility: Azienda Ospedaliero Careggi
city: Milan
country: Italy
facility: Istituto Nazionale Neurologico Carlo Besta
city: Rovigo
country: Italy
facility: Ospedale Civile di Rovigo
Study officials:
affiliation: Ospedale Bellaria
name: Alba A. Brandes, MD
role: STUDY_CHAIR
References: