A Phase I Study of Temozolomide, Thalidomide, and Lomustine (TTL) in Patients With Metastatic Melanoma in the Brain
Temozolomide works by blocking a tumor cell's ability to grow. Lomustine is also a
chemotherapy drug that works by killing tumor cells. Studies have shown that when lomustine
and temozolomide are given together, they decrease the amount of a certain protein, allowing
the tumor cells to be more easily killed. Thalidomide is a drug that alters the immune
system. it may also interfere with the development of tiny blood vessels that help support
tumor growth. Therefore, in theory, it may decrease or prevent the growth of cancer cells.
If you are found to be eligible to take part in this study, you will begin treatment. All 3
drugs will be taken by mouth at home. Each treatment cycle will last for 8 weeks. You will
take temozolomide once a day for 6 weeks followed by two weeks off. The best time to take
temozolomide is around bedtime, since you must not eat for at least 1 hour before and 1 hour
after taking it. The number of capsules you will take is based on your height and weight.
You must swallow all the temozolomide capsules at the same time with 8 ounces of water (do
not chew them).
You will take thalidomide every day for the entire 8-week cycle. Thalidomide should also be
taken near bedtime, usually 30 to 45 minutes before the temozolomide dose. If you are under
70 years of age, you will start at a set dose and take the same dose throughout the study.
If you are age 70 or over, the dose will start lower and will increase every 2 weeks until
you are taking the prearranged set dose that those under the age of 70 are taking. Your
doctor will be watching for side effects as the dose increases and may keep you at a lower
dose if necessary.
In the first groups of patients (3-6 patients per group, total up to 18 patients) to be
enrolled, each new group of participants will be given a higher dose of lomustine than the
previous group until the highest safe dose of lomustine is found or until 18 patients have
been enrolled. Responses to these doses will be evaluated. Once the best dose is found,
all future participants will receive that dose of lomustine.
You will take 2 doses of lomustine every 8 weeks. You will take the first dose of lomustine
on Day 1 of the 8-week cycle. You will take the second dose, which will be half as big as
the first dose, on Day 29 (the day after the first 4 weeks) of the 8-week cycle. The dose
of lomustine is also based on your height and weight. Lomustine should be swallowed and not
During treatment, every 2-4 weeks, you will have a complete physical exam and blood drawn
for testing (1-2 tablespoons). These tests will let the doctor know if the treatment should
be changed, briefly interrupted, or stopped. Women who are able to have children must have
a negative pregnancy test every week for the first 4 weeks if they have regular menstruation
and every 2 weeks if their periods are irregular.
At the end of 8 weeks, you will have x-rays or scans done again to see how the tumors have
responded. If they are the same size or have gotten smaller, you may continue the
treatment. You may stay on treatment as long as you are not having severe side effects and
your tumor is either staying the same size or getting smaller. Treatment will be stopped if
the tumors are getting bigger.
If you are withdrawn from the study for any reason you will be contacted by phone every
three months to learn how are you doing health wise.
This is an investigational study. None of the 3 drugs used in this study have been approved
by the FDA for the treatment of melanoma. Temozolomide has been approved for the treatment
of brain cancer. Thalidomide has not yet been approved for the treatment of cancer.
Lomustine is approved for the treatment of brain tumors and Hodgkin's disease. All of the
drugs are commercially available. Their use together in this study is experimental.
Up to 18 patients will take part in this Phase I portion of the study, and another 30
patients in Phase II if progresses, with up to 48 patients total. All will be enrolled at M.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD)
1 cycle (8 weeks) of therapy
Nicholas E. Papadopoulos, MD
M.D. Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|