Astrocytoma
Conditions
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.
Interventions
DRUGTemozolomide
Temozolomide orally once daily for 5 consecutive days followed by a 23 day rest period to complete a 28 day treatment cycle. In Cycle 1, temozolomide will be administered at 150 mg/m2/day; in Cycle 2 and subsequent cycles, it will be administered at 100, 150, or 200 mg/m2, depending on hematology test results and adverse events observed.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall response in Step 1 | 6 months |
| Incidence rate and severity of adverse events with administration of temozolomide in Step 1 | 7 months (during temozolomide administration for 6 months and follow-up for 1 month) |
Secondary
| Measure | Time frame |
|---|---|
| Safety in Step 2 | Up to 2 years |
| Neurological improvement in Step 1 | 6 months |
| Progression-free survival, overall survival, overall response, effect on neurological symptoms, and safety in Step 2 | 6 months |
| Progression-free survival in Step 2 | Up to 2 years |
| Overall response in Step 2 | Up to 2 years |
| Progression-free survival in Step 1 | 6 months |
| Overall survival in Step 1 | 6 months |
| Tumor response in Step 1 | 6 months |
| Overall survival in Step 2 | Up to 2 years |
| Effect on neurological symptoms in Step 2 | Up to 2 years |
Outcome results
None listed