This trial is active, not recruiting.

Condition malignant pleural mesothelioma
Treatment dasatinib
Phase phase 1
Target BCR-ABL
Sponsor M.D. Anderson Cancer Center
Collaborator Bristol-Myers Squibb
Start date March 2008
End date March 2018
Trial size 60 participants
Trial identifier NCT00652574, 2006-0935, NCI-2010-01505, W81XWH-07-1-0306


The goal of this clinical research study is to learn how dasatinib affects biomarker levels in patients with malignant pleural mesothelioma that may be able to be removed by surgery. The safety and effectiveness of this drug will also be studied.


Primary Objectives:

The primary objective of this novel phase I trial will be the level of biomarker modulation of p-Src Tyr 419 by induction dasatinib therapy in patients with resectable malignant pleural mesothelioma.

Secondary Objectives:

Secondary objectives include overall and progression-free survival, tumor radiographic and pathologic response, and safety-toxicity profiles. Exploratory analyses will include additional biomarker evaluation in pre- and post-treatment tumor specimens, and serum/platelet/pleural effusion biomarker modulation.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Dasatinib = BMS-354825, Sprycel
dasatinib BMS-354825
70 mg by mouth twice daily x 28 days, for up to 2 years after surgery.

Primary Outcomes

Modulation of biomarker p-Src Tyr419 expression
time frame: Weekly during treatment followed by 5-6 core biopsies during surgery.

Secondary Outcomes

Progression-free Survival
time frame: 3 Years, or until disease progression.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Patients with potentially resectable malignant pleural mesothelioma, IMIG stage I-III 2. Subject, age >/= 18 years 3. Any patient who is able to tolerate general anesthesia for the extended surgical staging and the definitive surgical resection. 4. No prior chemotherapy for mesothelioma within the last 3 years 5. No prior radiation to the area of primary disease. Radiation to chest wall port sites is acceptable. 6. No prior targeted biologic therapy (i.e. EGFR inhibitors, VEGF inhibitors) within the last 3 years 7. Adequate Organ Function: a) Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN), b) Hepatic enzymes (AST, ALT ) /= Lower Limit of Normal (LLN), d) Serum Creatinine < 1.5 time the institutional ULN, e) Hemoglobin, Neutrophil count, Platelets, PT, PTT all Grade 0-1 8. Ability to take oral medication (dasatinib must be swallowed whole) 9. Women of childbearing potential (WOCBP) must have: A negative serum or urine pregnancy test (sensitivity 450 msec), 3. Subjects with hypokalemia or hypomagnesemia if it cannot be corrected 5. History of significant bleeding disorder unrelated to cancer, including: a) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), b) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies), c) Ongoing or recent (

Additional Information

Official title Phase I Trial of Induction Dasatinib Therapy in Patients With Resectable Malignant Pleural Mesothelioma
Principal investigator Anne S. Tsao, MD
Description 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. Study Visits: 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. Surgery: 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 diaphragm. 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. Follow-up Visits: 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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.