Sarasar and Temodar for Glioblastoma Multiforme Patients
The goal of this clinical research study is to find the highest safe dose of the new drug Sarasar (lonafarnib) that can be given together with Temodar (temozolomide) in a continuous daily dosing regimen to patients with brain tumors. The second goal is to learn if these drugs given in combination can shrink or slow the growth of brain tumors.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/Ib Study of Sarasar and Temodar in Patients With Recurrent or Temodar-Refractory Glioblastoma Multiforme|
- Maximum tolerated dose (MTD) Sarasar when combined with Temodar in an alternating week schedule [ Time Frame: 28 Day Cycle ] [ Designated as safety issue: Yes ]MTD of Sarasar given with Temodar will be that dose at which fewer than one-third of participants experience dose limiting toxicity (DLT).
- 6-month Progression-Free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]Progression defined as 25% increase in sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Progression measured using combination of neurological examination and Magnetic Resonance Imaging (MRI) brain scan.
|Study Start Date:||December 2004|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Sarasar + Temodar
Sarasar Starting Dose: 100 mg by mouth twice a day, with water, for 7 consecutive days (Days 8-14 and Days 22-28). Cycle is 28 days.
Temodar 150 mg/m^2 by mouth once a day, after fasting one hour, for 7 consecutive days (Days 1-7 and Days 15-21). Cycle is 28 days.
Starting dose 100 mg by mouth twice a day, with water, for 7 consecutive days (days 8 through 14 and days 22 through 28). Cycle is 28 days.
Other Names:Drug: Temodar
150 mg/m^2 by mouth once a day, after fasting one hour, for 7 consecutive days (days 1 through 7 and days 15 through 21). Cycle is 28 days.
Other Name: Temozolomide
Temozolomide is a chemotherapy drug that works by attacking cancer cells, causing them to die. Lonafarnib 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 tumors.
If you are eligible to take part in the study, you will be given temozolomide and lonafarnib as treatment. The size of study drug doses being given will increase after every 3 participants are enrolled on the study, until the highest safe dose of each drug, when given in combination, is found.
If you are enrolled on the Phase Ib part of this study, you will be treated at the highest tolerable dose that was found in the Phase I part of the study. You will receive this dose of temozolomide on a 7-day on, 7-day off schedule. You will also receive Sarasar by mouth twice a day using a 7-day on, 7-day off schedule.
Temozolomide and lonafarnib will be taken by mouth in this study. You will take temozolomide once a day for 7 days every other week (Days 1-7 and 15-21). You must not eat for 1 hour before and after taking the drug; drinking water is allowed. During the alternate weeks (Days 8-14 and 22-28), you will take the lonafarnib tablet by mouth in the morning and evening, with water. You should not eat grapefruit or drink grapefruit juice while you are taking the study medication as this will affect how study medication is broken down in your body. This will be repeated every 28 days (1 study course). All treatment may be given on an outpatient basis, and so you will not require a hospital stay.
You may keep on taking temozolomide and lonafarnib for up to 24 courses (about 2 years). You will be taken off study if the disease gets worse or intolerable side effects occur. You may not receive any other treatment for cancer (including surgery) while taking part in this study.
You will come to the clinic to have a complete physical exam before each course of treatment. You will have a neurological exam within 14 days before every odd-numbered course (3, 5, 7, etc), or at any time that the doctor feels it is needed. Blood counts (about 1 teaspoon) will be done before every course of treatment and on Day 22 of each course. Blood chemistry tests and anticonvulsant levels, if applicable, (less than 1 tablespoon) will be repeated before each course of treatment. An MRI scan will be done before the odd-numbered (3, 5, 7, etc.) courses of treatment, or at any time that the doctor feels it is needed. Patients taking the blood thinner warfarin will have blood tests (less than 1 teaspoon) more often to check the effects of the drug.
Your doctor may decide to take you off combination treatment before 2 years and give you only the lonafarnib alone. If you continue to receive lonafarnib by itself without the addition of temozolomide, after having received a minimum of 1 year of the combination therapy, you will have routine blood (about 2-3 teaspoons) tests every 4 weeks and an MRI with clinic follow-up for physical and neurological exams every 3 months while receiving continuation treatment.
When you have finished the study treatment, you will have another complete physical and neurological exam. Blood tests (less than 2 tablespoons of blood) will be performed. Another MRI scan will be done.
This is an investigational study. Temozolomide is approved by the FDA for the treatment of some brain tumors. Lonafarnib is approved for research use only in the treatment of brain tumors. The use of these two drugs together is experimental. About 35 patients will take part in this study. All will be enrolled at MD Anderson.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00102648
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Mark R. Gilbert, MD||M.D. Anderson Cancer Center|