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)

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Glioma, Astrocytoma, Oligodendroglioma, Glioblastoma

Intervention / Treatment
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* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide<br>Temozolomide will be administered at a dose of 50 mg/m^2 for cycles of 28 days for 12 months or until progression. | Drug: Temozolomide<br>* Subjects will receive temozolomide 50 mg/m^2 for cycles of 28 days for 12 months or until progression<br>* Other names: SCH 52365;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Surviving at Six Months of Treatment Without Evidence of Disease Progression. | Progression-free survival as determined by Kaplan-Meier method. | 6 months |