the effects of continuous 28-day (28/28) temozolomide chemotherapy in subjects with recurrent malignant glioma who have failed the conventional 5-day (5/28) treatment (p04601)

Conditions: Glioma; Astrocytoma; Oligodendroglioma; Glioblastoma

Summary: the purpose of this non-randomized, open-label, multicenter, phase ii, 2-stage design, rescue study is to test the hypothesis that continuous 28-day oral dosing (28/28) with dose-intense temozolomide (50 mg/m\^2) for up to 12 months may overcome resistance and be effective in the management of adult patients with malignant glioma who have failed following at least 2 cycles (2 months) of conventional 5-day (5/28) cycles of high-dose temozolomide (150-200 mg/m\^2).


Eligibility criteria:
inclusion criteria: * adult patients, greater than 18 years old. * surgically confirmed diagnosis of malignant glioma, specifically anaplastic glioma (anaplastic astrocytoma \[aa\], anaplastic oligodendroglioma \[ao\], anaplastic oligoastrocytoma \[aoa\]) or glioblastoma multiforme (gbm). * must have completed at least 2 cycles (2 months) of conventional 5/28 temozolomide, with radiological evidence of progression. * gbm treated with concurrent chemoradiation with temozolomide according to the eortc/ncic (european organization for research \& treatment of cancer/national cancer institute of canada) protocol. * evidence of progression confirmed radiologically (ct \[computed tomography\] or mri \[magnetic resonance imaging\]). * patients must be enrolled within 2 weeks of last radiological confirmation of progression, except for patients undergoing surgical resection. * patients undergoing surgical resection for recurrent disease must be enrolled within 2 weeks of the post-surgical scan. * patients with no residual disease after surgery are allowed. * steroids dose should have been stabilized during the last 2 weeks prior to enrollment. * use of medically approved contraception in fertile males and females. * women of childbearing potential must have a negative urine or serum pregnancy test (urinary excretion or serum level of bhcg \[beta human chorionic gonadotropin\]) within 24 hours of inclusion in the study. * eastern cooperative oncology group (ecog) score of 0 or 1. * signed informed consent form. exclusion criteria: * gbm progression during the first 2 months of adjuvant temozolomide (5/28). * aa progression during the first 2 months of standard temozolomide therapy (5/28). * chemotherapy for the malignant glioma other than temozolomide. * more than one prior course of chemotherapy with temozolomide. * patient evolving from anaplastic glioma to gbm following primary therapy. * patient older than 70 years or who received no conventional chemoradiation regimen. * patient who received radiotherapy for recurrent disease. * patient with metastatic disease. * known human immunodeficiency virus (hiv) infection. * history of non-compliance to other therapies. * inadequate hematological, renal and hepatic function according to all of the following laboratory values (to be performed within 14 days, inclusive, prior to study inclusion): * absolute neutrophil count \<=1.5 ×10\^9/l; * platelets \<=100 ×10\^9/l; * hemoglobin \<90 g/l; * serum creatinine \>=1.5 times upper limit of laboratory normal (uln); * total serum bilirubin \>=1.5 times uln; * asat (ast \[aspartate aminotransferase\]) or alat (alt \[alanine aminotransferase) \>2.0 times uln; * alkaline phosphatase of \>2.5 times uln. * known chronic hepatitis b or hepatitis c infection. * any other serious medical condition, according to the medical judgment of the physician prior to inclusion in the study. * any medical condition that could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction). * other malignancies during the previous 5 years with the exception of surgically cured carcinoma in-situ of the cervix and basal cell carcinoma or non-melanoma skin cancer. * any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule as discussed with the patient before inclusion in the study.