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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)

Phase 2
Completed
Conditions
Astrocytoma
Interventions
Registration Number
NCT00783393
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Single armTemozolomideThe study consists of two steps: * Step 1, the therapeutic study phase, comprising six cycles of treatment with temozolomide, and * Step 2, the long-term treatment phase, where subjects with at least disease stabilization at the end of Step 1 may continue temozolomide treatment until unacceptable toxicity or disease progression occur, up to a maximum of 2 years from the start of treatment in Cycle 1.
Primary Outcome Measures
NameTimeMethod
Overall response in Step 16 months
Incidence rate and severity of adverse events with administration of temozolomide in Step 17 months (during temozolomide administration for 6 months and follow-up for 1 month)
Secondary Outcome Measures
NameTimeMethod
Neurological improvement in Step 16 months
Overall survival in Step 2Up to 2 years
Effect on neurological symptoms in Step 2Up to 2 years
Progression-free survival in Step 16 months
Overall survival in Step 16 months
Tumor response in Step 16 months
Progression-free survival, overall survival, overall response, effect on neurological symptoms, and safety in Step 26 months
Overall response in Step 2Up to 2 years
Progression-free survival in Step 2Up to 2 years
Safety in Step 2Up to 2 years
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