SCH 52365 Phase II Clinical Study: A Study on the Efficacy and Safety of Monotherapy With SCH 52365 in Patients With First Relapsed Anaplastic Astrocytoma (Study P03745)

Inclusion criteria

• Subject must have histologically confirmed anaplastic astrocytoma on the tentorium at first relapse, and satisfy the following:

• unequivocal evidence of tumor recurrence or aggravation by MRI scan after treatment for initial onset; the lesions must be measurable;
• anaplastic astrocytoma diagnosed histologically by the last pathological diagnostic tests (including initial diagnosis) prior to initial administration of temozolomide;
• tissue samples available for Central Pathologic Reviewer;
• pathologic diagnosis report by the study-conducting medical institution must be available for the sponsor.
• MRI-related criteria:

• MRI scan performed within 14 days before initial temozolomide administration;
• assessable tumor site confirmed by MRI;
• dosage of steroidal agents not increased within 7 days before MRI prior to initial temozolomide administration, except for postoperative subjects for first relapse;
• MRI performed at the Principal Investigator's study location or designated radiology facility during the study.
• Age >=18 years, either sex, inpatients or outpatients.
• Use of medically approved contraception methods in fertile subjects.
• Karnofsky performance status >=70.
• Adequate clinically laboratory values obtained within 14 days before initial temozolomide administration.
• Criteria regarding treatment of initial onset:

• tumor biopsy, regardless of tumor resection at initial diagnosis;
• prior radiation therapy;
• prior chemotherapy with up to one nitrosourea-containing regimen.
• Tumor may or may not have been surgically resected at first relapse, but residual measurable disease is required.
• For subjects who had surgical resection of tumor at first relapse:

• MRI scan must have been performed within 72 hours after surgery.
• the dose of steroidal agents must be reduced before temozolomide administration.
• Life expectancy >=12 weeks.
• Written informed consent obtained.

Exclusion criteria

• History of treatment with dacarbazine.
• Subjects who received chemotherapy within 6 weeks before initial temozolomide administration.
• Subjects who received interstitial radiotherapy or stereotactic radiosurgery.
• Subjects who completed radiotherapy within 12 weeks before initial temozolomide administration.
• Surgery at first relapse (including biopsy) within 1 week before initial temozolomide administration.
• Subjects not recovered from acute toxicity due to previous therapy.
• High-risk subjects with complication of diseases other than malignant tumor, or who require systemic administration of antibiotics for infection.
• Previous or concurrent malignancies at other sites.
• Pregnant or nursing women.
• Women of childbearing potential not using an effective method of contraception.
• Subjects previously treated with temozolomide.
• Participation in an ongoing clinical study, or in other clinical studies within 6 months before initial temozolomide administration.
• Subjects found inappropriate for the study by the investigator or subinvestigator.