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).

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.](streamdown:incomplete-link)

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf

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