Malignant Pleural MesotheliomaPhase 1NCT00652574
Dasatinib in Resectable Malignant Pleural Mesothelioma
A Phase 1 study testing Dasatinib in people with Malignant Pleural Mesothelioma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Mesothelioma
- What is being tested?
- Dasatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2008to 7 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with potentially resectable malignant pleural mesothelioma, IMIG stage I-III
- Subject, age >/= 18 years
- Any patient who is able to tolerate general anesthesia for the extended surgical staging and the definitive surgical resection.
- No prior chemotherapy for mesothelioma within the last 3 years
- No prior radiation to the area of primary disease. Radiation to chest wall port sites is acceptable.
- No prior targeted biologic therapy (i.e. EGFR inhibitors, VEGF inhibitors) within the last 3 years
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- Adequate Organ Function: a) Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN), b) Hepatic enzymes (AST, ALT ) </= 2.5 times the institutional ULN, c) Serum Na, K+, Mg2+, Phosphate and Ca2+>/= 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
- Ability to take oral medication (dasatinib must be swallowed whole)
- Women of childbearing potential (WOCBP) must have: A negative serum or urine pregnancy test (sensitivity </= 25IU HCG/L) within 72 hours prior to the start of study drug administration
- Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped
- Signed written informed consent including HIPAA according to institutional guidelines
Who cannot join
- Malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 3 years.
- Prior therapies to be excluded: any prior chemotherapy or targeted biologic therapy for mesothelioma used within the last 3 years
- Concurrent medical condition which may increase the risk of toxicity, including: a) Clinically-significant coagulation or platelet function disorder (e.g. known von Willebrand's disease) b) Any disease which requires persistent anticoagulation therapy (and the patient may not be taken off the anti-coagulation safely) with coumadin, factor Xa inhibitors, or heparin (low-molecular weight, standard)
- Cardiac Symptoms, consider the following: a) Uncontrolled angina, congestive heart failure or MI within (6 months), b) Diagnosed congenital long QT syndrome: 1. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), 2. Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec), 3. Subjects with hypokalemia or hypomagnesemia if it cannot be corrected
- 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 (</= 3 months) significant gastrointestinal bleeding
- Concomitant Medications, consider the following prohibitions: a) Drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib): A) quinidine, procainamide, disopyramide, B) amiodarone, sotalol, ibutilide, dofetilide, C) erythromycin, clarithromycin, D) chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide E) cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine. F) moxifloxacin, levofloxacin
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- The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not recommended.The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy.a)Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy,b)Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia,c)Patient may not be receiving any prohibited CYP3A4 inhibitors,d)Patient may not be receiving any alternative herbal remedies during the dasatinib treatment period
- Women: a) are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or, b) have a positive pregnancy test at baseline, or c) are pregnant or breastfeeding, d) Sexually active women of childbearing potential (WOCBP) must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized.,
- -continued from exclusion #8-: e) Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy., f) All WOCBP MUST have a negative pregnancy test prior to first receiving dasatinib. If the pregnancy test is positive, the patient must not receive dasatinib and must not be enrolled in the study.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase I Trial of Induction Dasatinib Therapy in Patients With Resectable Malignant Pleural Mesothelioma
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.
This research study is financially supported by the United States Department of Defense.
Read the detailed 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 MD Anderson.
- Conditions
- Malignant Pleural Mesothelioma
- Being tested
- Dasatinib
- Keywords
- Malignant Pleural Mesothelioma, Dasatinib, BMS-354825, Sprycel, MPM
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called BMS-354825, Sprycel
70 mg by mouth twice daily x 28 days, for up to 2 years after surgery.
| Study group | Role | What they receive |
|---|---|---|
| Dasatinib | Experimental | Dasatinib = BMS-354825, Sprycel Receives: Drug: Dasatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modulation of biomarker p-Src Tyr419 expression
McNemar's test used to compare the p-Src Tyr 419 expression before and after dasatinib treatment. The magnitude of modulation tested and quantified via paired-t test and Wilcoxon signed-rank test. For continuous data, paired-t test used for testing the biomarker modulation pre- and post-treatment.
Measured: Weekly during treatment followed by 5-6 core biopsies during surgery.
Secondary outcomes (1)
Progression-free Survival
Kaplan-Meier method used to estimate the distribution of time-to-event-endpoints. Pearson and Spearman's correlation coefficients computed to correlate baseline biomarker values and biomarker modulation with participant's medical demographic variables as well as clinical outcomes.
Measured: 3 Years, or until disease progression.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2008 (estimated)
- Study start12 Mar 2008
- Primary completion7 Oct 2022
- Study completion7 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Pleural MesotheliomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Anne S. Tsao, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00652574
- Sponsor's protocol ID
- 2006-0935
- Other IDs
- NCI-2010-01505, W81XWH-07-1-0306
- Status last verified
- Oct 2022
- First submitted
- 27 Mar 2008
- Last updated
- 31 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Induction Dasatinib Therapy in Patients With Resectable Malignant Pleural Mesothelioma
- ClinicalTrials.gov ID
- NCT00652574
- Acronym / sponsor ID
- 2006-0935
- Conditions
- Malignant Pleural Mesothelioma
- Keywords
- Malignant Pleural Mesothelioma, Dasatinib, BMS-354825, Sprycel, MPM
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, United States Department of Defense
- Study start
- 12 Mar 2008 (actual)
- Primary completion
- 7 Oct 2022 (actual)
- Study completion
- 7 Oct 2022 (actual)
- First posted
- 3 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
This research study is financially supported by the United States Department of Defense.
Detailed 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 MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dasatinib | Experimental | Drug: DasatinibDasatinib = BMS-354825, Sprycel |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with potentially resectable malignant pleural mesothelioma, IMIG stage I-III
- Subject, age >/= 18 years
- Any patient who is able to tolerate general anesthesia for the extended surgical staging and the definitive surgical resection.
- No prior chemotherapy for mesothelioma within the last 3 years
- No prior radiation to the area of primary disease. Radiation to chest wall port sites is acceptable.
Key exclusion criteria (10 listed)
- Malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 3 years.
- Prior therapies to be excluded: any prior chemotherapy or targeted biologic therapy for mesothelioma used within the last 3 years
- Concurrent medical condition which may increase the risk of toxicity, including: a) Clinically-significant coagulation or platelet function disorder (e.g. known von Willebrand's disease) b) Any disease which requires persistent anticoagulation therapy (and the patient may not be taken off the anti-coagulation safely) with coumadin, factor Xa inhibitors, or heparin (low-molecular weight, standard)
- Cardiac Symptoms, consider the following: a) Uncontrolled angina, congestive heart failure or MI within (6 months), b) Diagnosed congenital long QT syndrome: 1. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), 2. Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec), 3. Subjects with hypokalemia or hypomagnesemia if it cannot be corrected
- 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 (</= 3 months) significant gastrointestinal bleeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DasatinibAlso: BMS-354825, Sprycel70 mg by mouth twice daily x 28 days, for up to 2 years after surgery. | Drug | Dasatinib |
Primary outcome
Modulation of biomarker p-Src Tyr419 expression
Time frame: Weekly during treatment followed by 5-6 core biopsies during surgery.
McNemar's test used to compare the p-Src Tyr 419 expression before and after dasatinib treatment. The magnitude of modulation tested and quantified via paired-t test and Wilcoxon signed-rank test. For continuous data, paired-t test used for testing the biomarker modulation pre- and post-treatment.
1 secondary outcome
Progression-free Survival
Time frame: 3 Years, or until disease progression.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2022.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne S. Tsao, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dasatinib in people with Malignant Pleural Mesothelioma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modulation of biomarker p-Src Tyr419 expression (time frame: Weekly during treatment followed by 5-6 core biopsies during surgery.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2022.