The Temozolomide RESCUE Study: A Phase II Trial of Continuous (28/28) Dose-intense Temozolomide (CDIT) Chemotherapy After Progression on Conventional 5/28 Day Temozolomide in Patients With Recurrent Malignant Glioma
- 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
- 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.
- 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
- 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
- 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.