Clinical trial NCT00039364: Imatinib Mesylate in Treating Patients With Gliomas
Official title: Open Label Phase II Study On STI571 (Glivec) Administered As A Daily Oral Treatment In Gliomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult pilocytic astrocytoma
adult subependymoma
adult giant cell glioblastoma
adult gliosarcoma
adult diffuse astrocytoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells and slow the growth of the tumor.

PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have gliomas.

Detailed description: OBJECTIVES:

* Determine the therapeutic activity of imatinib mesylate (in terms of objective response and progression-free survival at 6 months) in patients with gliomas.
* Determine the safety of this drug in these patients.
* Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to glioma (glioblastoma multiforme vs anaplastic oligodendroglioma or mixed oligoastrocytoma vs anaplastic astrocytoma or recurrent low-grade astrocytoma).

Patients receive oral imatinib mesylate once or twice daily. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 6 months and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 77 patients (29 patients with glioblastoma multiforme, 24 patients with anaplastic oligodendroglioma or mixed oligoastrocytoma, and 24 patients with anaplastic astrocytoma or recurrent low-grade astrocytoma) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed glioblastoma multiforme

  * Recurrent disease by CT scan or MRI
  * No prior chemotherapy OR
  * No more than 1 prior chemotherapy regimen in adjuvant setting or for recurrent disease OR
* Histologically or cytologically confirmed anaplastic oligodendroglioma, mixed oligoastrocytoma, anaplastic astrocytoma, or recurrent low-grade astrocytoma

  * Failed prior radiotherapy
  * No more than 1 prior chemotherapy regimen

    * Failed adjuvant chemotherapy OR
    * Failed first-line chemotherapy
* At least 1 bidimensionally measurable target lesion

  * At least 2 cm on contrast-enhanced CT scan or MRI

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Neutrophil count at least 2,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* AST and ALT no greater than 2.5 times ULN
* Alkaline phosphatase no greater than 2.5 times ULN

Renal:

* Creatinine less than 1.7 mg/dL

Cardiovascular:

* Cardiac function normal
* No ischemic heart disease within the past 6 months
* Normal 12-lead ECG

Other:

* No other prior or concurrent malignancy except cone-biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer
* No unstable systemic disease
* No active uncontrolled infection
* No psychological, familial, sociological, or geographical condition that would preclude study compliance
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent anticancer biologic agents
* No concurrent cytokines (e.g., filgrastim \[G-CSF\] or sargramostim \[GM-CSF\])

Chemotherapy:

* See Disease Characteristics
* At least 4 weeks since prior chemotherapy (6 weeks for nitrosourea)
* No concurrent chemotherapy

Endocrine therapy:

* Must be on stable or decreasing dose of corticosteroids for at least 2 weeks

Radiotherapy:

* See Disease Characteristics
* At least 3 months since prior brain irradiation
* No prior high-dose radiotherapy (more than 65 Gy), stereotactic radiosurgery, or internal radiotherapy unless the recurrence is histologically confirmed
* No concurrent radiotherapy

Surgery:

* Prior surgery for primary brain tumor within the past 3 months allowed provided one of the following conditions are present:

  * Postoperative imaging within 72 hours after surgery shows a clearly limited target lesion of at least 2 cm
  * Postoperative follow-up shows a progressive and measurable target lesion
  * A second measurable target lesion is present outside the surgical area

Other:

* No concurrent warfarin or other anticoagulants
* No other concurrent anticancer agents
* No other concurrent investigational agents

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Kaiser Franz Josef Hospital
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer, Georges-Francois Leclerc
city: Nantes-Saint Herblain
country: France
facility: CRLCC Nantes - Atlantique
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Rotterdam
country: Netherlands
facility: Daniel Den Hoed Cancer Center at Erasmus Medical Center
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre
state: Scotland
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Eric Raymond, MD, PhD
role: STUDY_CHAIR
affiliation: Daniel Den Hoed Cancer Center at Erasmus Medical Center
name: Martin J. van Den Bent, MD
role: STUDY_CHAIR
References:
citation: Raymond E, Brandes AA, Dittrich C, Fumoleau P, Coudert B, Clement PM, Frenay M, Rampling R, Stupp R, Kros JM, Heinrich MC, Gorlia T, Lacombe D, van den Bent MJ; European Organisation for Research and Treatment of Cancer Brain Tumor Group Study. Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study. J Clin Oncol. 2008 Oct 1;26(28):4659-65. doi: 10.1200/JCO.2008.16.9235.
citation: Raymond E, Brandes A, Van Oosterom A, et al.: Multicentre phase II study of imatinib mesylate in patients with recurrent glioblastoma: an EORTC: NDDG/BTG Intergroup study. [Abstract] J Clin Oncol 22 (Suppl 14): A-1501, 2004.