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)(COMPLETED)

• Overall response in Step 1 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Incidence rate and severity of adverse events with administration of temozolomide in Step 1 [ Time Frame: 7 months (during temozolomide administration for 6 months and follow-up for 1 month) ] [ Designated as safety issue: Yes ]

• Progression-free survival in Step 1 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Overall survival in Step 1 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Tumor response in Step 1 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Neurological improvement in Step 1 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Progression-free survival, overall survival, overall response, effect on neurological symptoms, and safety in Step 2 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Progression-free survival in Step 2 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
• Overall survival in Step 2 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
• Overall response in Step 2 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
• Effect on neurological symptoms in Step 2 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
• Safety in Step 2 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

The primary purpose of the study is to evaluate the efficacy (overall response) and safety of temozolomide in Step 1 at the dose and regimen approved in the US and the EU countries (28 day cycles of temozolomide at 150 to 200 mg/m2 once daily for 5 consecutive days with a 23 day rest period) in patients with anaplastic astrocytoma at first relapse.

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.