Dasatinib in Resectable Malignant Pleural Mesothelioma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00652574
First received: March 27, 2008
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

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.

Objectives:

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.


Condition Intervention Phase
Malignant Pleural Mesothelioma
Drug: Dasatinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Induction Dasatinib Therapy in Patients With Resectable Malignant Pleural Mesothelioma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Modulation of biomarker p-Src Tyr419 expression [ Time Frame: Weekly during treatment followed by 5-6 core biopsies during surgery. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall and progression-free survival times [ Time Frame: 3 Years, or until disease progression. ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: March 2008
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib
Dasatinib = BMS-354825, Sprycel
Drug: Dasatinib
70 mg by mouth twice daily x 28 days, for up to 2 years after surgery.
Other Names:
  • BMS-354825
  • Sprycel

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ) </= 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
  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 </= 25IU HCG/L) within 72 hours prior to the start of study drug administration
  10. 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
  11. Signed written informed consent including HIPAA according to institutional guidelines

Exclusion Criteria:

  1. Malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 3 years.
  2. Prior therapies to be excluded: any prior chemotherapy or targeted biologic therapy for mesothelioma used within the last 3 years
  3. 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)
  4. 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
  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 (</= 3 months) significant gastrointestinal bleeding
  6. 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
  7. 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
  8. 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.,
  9. -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.
  10. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00652574

Locations
United States, Texas
UT MD . Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: Anne S. Tsao, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00652574     History of Changes
Other Study ID Numbers: 2006-0935, NCI-2010-01505
Study First Received: March 27, 2008
Last Updated: February 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Malignant Pleural Mesothelioma
Dasatinib
BMS-354825
Sprycel
MPM

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014