Phase I Safety Study of the Combination of Lenalidomide and Dacarbazine (DTIC) in Patients With Metastatic Malignant Melanoma Previously Untreated With Systemic Chemotherapy (CC-5013-MEL-003)
Lenalidomide is related to a drug called Thalidomide, which is not widely used because of
certain side effects. Lenalidomide belongs to a family of drugs that work by acting on the
body's immune system, so that it makes more "anti-inflammatory" cells. This type of cell is
normally found in the body and is believed to help reduce the growth of cancer cells and
slow down the production of new cancer cells.
DTIC is an anti-cancer drug. It is designed to cause cancer cell death by creating DNA
breaks in the nucleus of the cells.
Before you can start treatment on this study, you will have what are called "screening
tests". These tests will help the doctor decide if you are eligible to take part in the
study. You will be asked questions about your medical history, and you will have a complete
physical exam, which will included measurements of your temperature, pulse, blood pressure,
respiratory (breathing) rate, weight and height. You will be asked about any surgeries you
have had and any medications you are taking. Your ability to perform daily activities will
be checked through simple physical tests (such as walking or squeezing a ball). You will
also have blood drawn (about 1 tablespoon) for routine tests and tests to measure your
You will have an electrocardiogram (ECG - a test that measures the electrical activity of
the heart). You will have a chest x-ray and CT scans of the chest, abdomen and pelvis
(below the waist). You will be required to have a MRI or CT scan of the brain. If your
doctor feels it is necessary, you may need CT scans of the head and neck or a bone scan. To
perform the bone scan, a small dose of radioactive technetium is administered intravenously
(IV--through a needle in your vein). The technetium will collect in the areas of bone
involved with metastatic cancer to "light up" these areas on the bone scan. The results of
these tests will show if you are eligible to participate in the study. Women who are able
to have children must have a negative blood pregnancy test.
If you are still eligible to take part in the study, you will begin study treatment. You
will take Lenalidomide by mouth every day for 2 weeks, followed by 1 week of "rest." This
21-day period is referred to as one "study cycle." You should only take Lenalidomide on an
empty stomach. You should fast for 1 hour before and after taking Lenalidomide.
DTIC will be given by IV on Day 1 of every study cycle. Three dose levels of DTIC will be
tested during this study. The first 3 participants will be given the first (lowest) dose
level of DTIC. After the safety of this dose of DTIC is confirmed at the starting dose
level, the next 3 to 6 participants will be given the second dose level of DTIC. After the
safety of this new dose level is confirmed, the dose of DTIC will be increased to the third
(highest) dose level tested in this study. When the highest DTIC dose is found that has the
fewest side effects when given with Lenalidomide, 10 more patients will be treated at this
best dose level. Patients on the lowest dose level will not have their doses changed once
the highest well tolerated dose is found. Once a patient starts on a dose, it will not be
You will receive treatment with Lenalidomide and DTIC on an outpatient basis at UT M.D.
Anderson Cancer Center. At the start of each 21-day study cycle, you will come in to the
clinic to receive a 14-day supply of Lenalidomide, and you will receive your dose of DTIC by
IV. You will be provided with a study drug diary each time you are given your supply of
Lenalidomide, to write down any side effects you experience.
During each study visit, you will have a physical exam (including measuring your weight),
and your medical history will be recorded. Your doctor will ask you about any side effects
you are experiencing. You should bring your study drug diary, any unused medication, and
empty packages of medication to each study visit. Women who are able to have children will
have a pregnancy test performed during the study visit at the beginning of each study cycle.
You will have blood drawn (about 1 tablespoon) for routine tests. You will also repeat the
performance status tests.
During your study visit at the beginning of Cycle 3 (about 6 weeks after starting
treatment), you will be checked to see if the disease is responding to treatment. You will
have a chest x-ray and CT scans of the chest, abdomen and pelvis. If your doctor feels it
is necessary, you will also have an EKG for the heart and MRI of the brain. These tests may
be done more often if your doctor feels it is necessary.
You will continue to receive treatment as long as the disease is shrinking or does not get
worse, and the study doctor decides that it is safe to do so. You will be taken off study
if the disease progresses or intolerable side effects occur.
If you are taken off study for any reason, you will be scheduled for a final study visit.
You will have a physical exam and will be checked for side effects related to the study
treatment. You will have a chest x-ray, CT scans, an ECG, and possibly an MRI as well.
You will have blood drawn (about 1 tablespoon) for routine tests. You will be asked about
any new symptoms that you may have experienced after the treatment was stopped.
This is an investigational study. DTIC has been approved by the FDA for the treatment of
metastatic melanoma. The FDA has authorized Lenalidomide for use in research only. Up to 28
participants will take part in this study. All will be enrolled at M. D. Anderson.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To find out the highest safe dose of DTIC that can be given in combination with a steady dose of Lenalidomide, to patients with malignant melanoma that has spread to other parts of the body and has not been treated with chemotherapy.
Agop Y. Bedikian, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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