Ph I Oral Topotecan and Temozolomide for Patients With Malignant Gliomas

Study Overview
=================
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.

Official Title
-----------------
Phase I Trial of Oral Topotecan Plus Temodar in the Treatment of Patients With Malignant Gliomas

Conditions
-----------------
Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma

Intervention / Treatment
-----------------
* Drug: Oral Topotecan and Temodar


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Topotecan and Temodar<br>Two separate strata to accrue independently. Stratum 1: Patients taking receiving Dilantin, Tegretol, Trileptal or Phenobarbital. Stratum 2: Patients on anti-convulsants other than Dilantin, Tegretol, Trileptal or Phenobarbital or patients not on any anti-convulsants | Drug: Oral Topotecan and Temodar<br>* 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.<br>* Other names: Topotecan - Hycamtin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety & efficacy |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Temodar, Temozolomide, Topotecan, Hycamtin, Malignant Gliomas, Brain tumor, Anaplastic astrocytoma, AA, GBM, Glioblastoma Multiform, Gliosarcoma