Dasatinib in Resectable Malignant Pleural Mesothelioma

NCT00652574 | Completed Phase 1 FDA Drug

• 3 other identifiers: 2006-0935NCI-2010-01505W81XWH-07-1-0306
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief 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. This research study is financially supported by the United States Department of Defense.

Conditions

Malignant Pleural Mesothelioma

Keywords

Malignant Pleural Mesothelioma; Dasatinib; BMS-354825; Sprycel; MPM

Outcome Measures

Primary Outcomes (1)

• 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.

  Weekly during treatment followed by 5-6 core biopsies during surgery.

Secondary Outcomes (1)

• Progression-free Survival

  3 Years, or until disease progression.

Study Arms (1)

Dasatinib

EXPERIMENTAL

Dasatinib = BMS-354825, Sprycel

Drug: Dasatinib

Interventions

Dasatinib DRUG

70 mg by mouth twice daily x 28 days, for up to 2 years after surgery.

Also known as: BMS-354825, Sprycel

Dasatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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.,
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• United States Department of Defense: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Anne S. Tsao, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2008
• First Posted: April 3, 2008
• Study Start: March 12, 2008
• Primary Completion: October 7, 2022
• Study Completion: October 7, 2022
• Last Updated: October 31, 2022

Record last verified: 2022-10

Locations

US (1)