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)

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

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.