Phase I/II Evaluation Temozolomide and Farnesyl Transferase Inhibitor ZARNESTRA (R115777) for the Treatment of Recurrent and Progressive Glioblastoma Multiforme
Temozolomide works by killing cancer cells. R115777 is a new drug that may slow down the
growth of cancer cells. Used in combination, the two drugs may control the growth of brain
Before treatment starts, patients will have a complete exam, including measurement of height
and weight. Blood tests (less than 2 tablespoons of blood) will be performed. A MRI scan
will be done. Women who are able have children must have a negative blood pregnancy test.
Temozolomide and R115777 will both be taken by mouth. Participants in this study will take
temozolomide once a day for 7 days every other week (Days 1-7 and 15-21). This will be
repeated every 28 days (1 course). Patients must not eat for 1 hour before and after
taking the drug; drinking water is allowed. All treatment may be given on an outpatient
During the alternate weeks (Days 8-14 and 22-28), participants will take R115777 tablets by
mouth in the morning and evening with food. At the beginning of the study, groups of 3
participants each will take increasing doses of both R115777 and temozolomide until the
highest safe dose of each drug, when given in combination, is found. Participants entering
the study after the highest safe dose is found will receive that dosage.
If tumors do not grow and serious side effects do not occur, participants may keep on taking
temozolomide and R115777 for up to 2 year. If your physician thinks it is advisable,
treatment may continue with R115777 alone after that time. In this case, routine blood
tests for counts, liver and kidney function (less than 2 tablespoons) will be repeated every
4 weeks and MRI scans, physical, and neurological exams will be done every 8 weeks.
Participants may not receive any other treatment for cancer (including surgery) while taking
part in this study.
Participants will come to the clinic to have a complete physical and neurological exam and
blood tests (less than 2 tablespoons of blood) before each course. Blood tests will be
repeated once a week for the first 2 courses of treatment and then on Days 14 and 28 of each
later course. A MRI scan will be done before the odd-numbered (3, 5, 7, etc.) courses of
treatment or at any time clinically indicated.
At the end of the study, participants will have another complete physical exam. Blood tests
(less than 2 tablespoons of blood) will be performed. A MRI scan will be done.
This is an investigational study. Temozolomide is approved by the FDA for the treatment of
some brain tumors and is commercially available. R115777 is approved for research use only
in the treatment of brain tumors. The use of these two drugs together is experimental.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximal Tolerating Dose (MTD for Phase I)
Phase I Dose limiting toxicity evaluation at end of first cycle based on blood tests every two weeks and participants' subjective and objective symptoms. Start Dose Level 100 mg/m² Temozolomide once daily + 400 mg ZARNESTRA twice daily; Dose Level 1 100 mg/m² Temozolomide once daily + 500 mg ZARNESTRA twice daily; Dose Level 2 150 mg/m² Temozolomide once daily + 500 mg ZARNESTRA twice daily; Dose Level 3 150 mg/m² Temozolomide once daily + 600 mg ZARNESTRA twice daily; Dose Level 4 150 mg/m² Temozolomide once daily + 800 mg ZARNESTRA twice daily
End of first cycle (4 weeks) evaluation
Mark R. Gilbert
MDAnderson Cancer Center
United States: Food and Drug Administration
|MD Anderson Cancer Center||Houston, Texas 77030-4096|