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)
Condition: Glioma; Astrocytoma; Oligodendroglioma; Glioblastoma
MeSH terms: Glioblastoma; Glioma; Astrocytoma; Oligodendroglioma
Intervention: Temozolomide
Intervention description: Subjects will receive temozolomide 50 mg/m^2 for cycles of 28 days for 12 months or until progression
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 120.0
Sex: All
Minimum age: 19 Years
Maximum age: 70 Years
Healthy volunteers: No

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.