Phase I Trial of Induction Dasatinib Therapy in Patients With Resectable Malignant Pleural Mesothelioma
The Study Drug:
Dasatinib is designed to decrease the activity of one or more proteins that are responsible
for the uncontrolled growth of tumor cells. This may cause the tumor cells to die.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take 2 dasatinib
tablets by mouth 2 times a day for the 4 weeks before surgery (in the morning and 12 hours
later). Dasatinib may be taken with or without food, but should be swallowed with at least 1
cup (8 ounces) of water. A light meal is not required, but may help you avoid getting a
stomach ache when you take your dose. Tablets must be swallowed whole and may not be
broken. If vomiting occurs within 30 minutes of swallowing the tablet(s), you can take
another dose. If you miss a dose of dasatinib, take it as soon as you remember on the same
day. If you miss taking your dose for 12 hours, take your regular dose the next scheduled
day (do not take double your regular dose to make up for the missed dose). You will be given
a "pill diary" to write down when you take the study drug. You will be shown how to fill it
out and asked to bring the diary with you to each clinic visit.
On Days 21 and 28, the following tests and procedures will be performed:
- You will have a physical exam, including measurement of vital signs and weight.
- You will also have a test to check the amount of oxygen in your blood.
- Blood (about 3-4 teaspoons) will be drawn for routine tests.
- You will have a performance status evaluation.
- You will have an ECG.
- Blood (about 1-2 teaspoons) will be drawn to check your how well your blood clots.
- You will have a PET scan to check the status of the disease. This PET scan will be
before your surgery, the study doctor will tell you when this will be performed.
After you have taken dasatinib for 28 days, you will have surgery to remove the tumor. You
will continue to take the dasatinib until midnight the night before the surgery. Depending
on the status of the disease, you will have either a pleurectomy or extrapleural
pneumonectomy. You will be given a separate consent for these procedures, which will
describe the surgery and any risks in detail.
Pleurectomy is the surgical procedure to remove the parietal pleura (the outermost lining
around the lungs).
An extrapleural pneumonectomy is a surgical procedure that removes portions of the lung, the
parietal pleura (the lining of the lung), the pericardium (the lining of the heart), and the
During surgery, 5-6 core biopsies, if possible, will be taken from different areas of the
tumor for biomarker testing.
For the CT-guided core biopsy of the lung, a tissue sample is withdrawn from an organ or
suspected tumor mass using a very thin needle and a syringe. The needle is guided while
being viewed by the physician on a CT scan.
Length of Study:
After surgery, your doctor will decide the type of treatment you should receive for your
condition. If the disease responded well to the 4 weeks of dasatinib, you may be eligible
to continue taking dasatinib once a day starting 4-6 weeks after your surgery. The doctor
may also decide that you can take dasatinib once a day starting 4-6 weeks after receiving
radiation therapy. You may continue to take dasatinib as long as you are benefitting. You
will be taken off study if intolerable side effects occur or the disease gets worse.
If you continue to receive the study drug after surgery, you will have a physical exam and a
PET or CT scan every 8 weeks.
If you are taken off study for any reason, you will continue to be followed by the study
team to see how you are doing.
This is an investigational study. Dasatinib is an investigational agent and ongoing
clinical trials are using this drug in malignant mesothelioma. However, these studies have
only recently started, and there is no information so far that shows the drug is effective
in malignant mesothelioma. Dasatinib is FDA approved and commercially available for the
treatment of acute lymphoid and chronic myeloid leukemia. However, its use in this research
study is investigational.
Up to 60 participants will take part in this study. All will be enrolled at M. D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Modulation of biomarker p-Src Tyr419 expression
Weekly during treatment followed by 5-6 core biopsies during surgery.
Anne S. Tsao, MD
M.D. Anderson Cancer Center
United States: Institutional Review Board
|UT MD . Anderson Cancer Center||Houston, Texas 77030|