Anaplastic Astrocytoma, Glioblastoma, Gliosarcoma
Conditions
Keywords
Temodar, Temozolomide, Topotecan, Hycamtin, Malignant Gliomas, Brain tumor, Anaplastic astrocytoma, AA, GBM, Glioblastoma Multiform, Gliosarcoma
Brief summary
Objectives: * To determine the maximum tolerated dose of oral topotecan when administered with Temodar to patients with malignant glioma * To characterize any toxicity associated with the combination oral topotecan and Temodar. * To observe patients for clinical antitumor response when treated with oral topotecan and Temodar.
Detailed description
Subjects are patients with glioblastoma (GBM), anaplastic astrocytoma (AA) or grade 3 or greater WHO astrocytic, oligodendroglial or mixed glial tumors, which were initially diagnosed by histologic examination of biopsy/resection. Modified classical 3+3 phase I design used to determine maximum tolerated dose of topotecan in combination with Temodar.
Interventions
DRUGOral Topotecan and Temodar
Temozolomide is taken by mouth once day, every day for 5 consecutive days at dose of 200 mg/m2/day. Oral Topotecan will be taken daily for 5 consecutive days beginning 12-24 hrs after 1st dose of Temozolomide. Dose escalation of Oral Topotecan will be carried out in cohorts of 3 new subjects beginning w dose level 1 @ 0.75 mg/m2/dose.
Sponsors
GlaxoSmithKline
Schering-Plough
Katy Peters
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
* Histology: GBM, AA or grade 3 or greater WHO astrocytic, oligodendroglial or mixed glial tumors which were initially diagnosed by histologic exam of biopsy/resection * Age: \> or equal to 18 years * Performance Status: Karnofsky Performance Status \> or equal to 60% at study entry. * Renal Function: Serum creatinine \< 1.5 mg/dl or creatinine clearance \> 60 ml/dL. * Hematologic Status: The following baseline studies will be required before entry: total granulocyte count \> or equal to 1000/microliter; platelet count \> 100,000/microliter * Hepatic Function: Serum SGOT & total bilirubin \< or equal to 2.5 times ULN. * Note: All lab parameters must have been obtained within 1 week of registration * Consent: Signed informed consent, approved by IRB, will be obtained prior to initiating treatment * Corticosteroids: For patients currently on corticosteroids, patients should be on stable dose for 1 week prior to study entry, if clinically possible. * Prior Therapy: Interval of at least 2 weeks between prior surgical resection or prior radiotherapy (XRT) or 1 week from completion of chemotherapy and all toxicities are \< or equal to grade 1 & enrollment on this protocol unless there is unequivocal evidence of progressive disease. * Patients with Reproductive Potential: Patients must agree to practice effective birth control measures while on study and for 2 months after completing therapy
Exclusion criteria
* Pregnant or breast feeding women or women or men with reproductive potential not practicing adequate contraception. This therapy may be associated with potential toxicity to the fetus or child that exceeds minimum risks necessary to meet health needs of mother * Active infection requiring intravenous antibiotics * Prior failure with either topotecan or temozolomide
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| maximum tolerated dose | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Safety & efficacy | 6 months |
Countries
United States
Outcome results
None listed