Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma

NCT ID: NCT00509041

Last Updated: 2016-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2012-12-31

Brief Summary

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with previously treated malignant mesothelioma.

Detailed Description

OBJECTIVES:

Primary

• To determine the rate of progression-free survival (PFS) at 24 weeks (or 5.5 months) in patients with malignant mesothelioma treated with dasatinib.

Secondary

• To determine the response rate (partial response [PR] and complete response [CR]) in patients with malignant mesothelioma treated with dasatinib.
• To determine the response duration in patients with malignant mesothelioma treated with dasatinib.
• To describe the overall survival (OS) of patients with malignant mesothelioma treated with dasatinib.
• To describe the toxicity profile of dasatinib in patients with malignant mesothelioma.
• To determine whether the amount of expression of EphA2 and PDGFRβ, as measured by immunohistochemistry from tumor specimens, correlates with PFS in patients with malignant mesothelioma.
• To determine whether plasma levels of VEGF and PDGFRβ, serum levels of CSF-1, and soluble mesothelin-related protein correlate with PFS in patients with malignant mesothelioma.
• To determine whether inhibition of Src phosphorylation in PBMC correlates with PFS.
• To assess inhibition of phosphorylation of Src, EphA2, and PDGFRβ in tumor tissue by dasatinib.

OUTLINE: Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection periodically for correlative studies. Tumor tissue samples are analyzed for EphA2 and PDGFRβ expression by immunohistochemistry. Tumor tissue samples may also be analyzed for phosphorylation of Src, EphA2, and PDGFRβ by western blot. Blood samples are analyzed for concentration of VEGF and PDGF by quantitative sandwich enzyme immunoassay technique; mesothelin-related protein level by Mesomark® assay; CSF-1 level by ELISA assay; and phosphorylation of Src by phospho-Src (pTyr418) human ELISA.

After completion of study treatment, patients are followed at least every 2 months for 1 year, then every 4 months for 1 year, then every 6 months for 1 year.

Conditions

Malignant Mesothelioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dasatinib

Use of dasatinib in treatment of pts with previously treated malignant mesothelioma

Group Type: EXPERIMENTAL

dasatinib

Intervention Type: DRUG

50 mg PO bid

Interventions

dasatinib

50 mg PO bid

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• No known brain metastases
• May be registered on CALGB-150707 companion study

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Granulocytes ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Total bilirubin ≤ 2 x upper limit of normal (ULN)
• AST (SGOT) ≤ 2.5 x ULN
• Creatinine clearance ≥ 60 mL/min
• INR < 1.5
• PTT < 40 seconds
• QTc < 450 msec
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No significant cardiac disease, including any of the following:

• New York Heart Association (NYHA) class III-IV congestive heart failure (CHF)
• Unstable angina
• Myocardial infarction or ventricular tachyarrhythmia within 6 months of study entry
• Ejection fraction less than institutional normal (in patients with a history of CHF or currently with NYHA class I or II CHF)
• Prolonged QTc > 450 msec (Fridericia correction)
• Major conduction abnormality, unless a cardiac pacemaker is present
• Hypokalemia or hypomagnesemia that cannot be corrected
• No history of significant bleeding disorder unrelated to cancer, including any of the following:

• Congenital bleeding disorder (e.g., von Willebrand disease)
• Acquired bleeding disorder within the past year (e.g., acquired anti-factor VIII antibodies)
• Ongoing or recent (≤ 3 months) significant GI bleeding or hemoptysis
• No requirement for supplemental oxygen (i.e., pulse oximetry < 89% at rest)

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior pemetrexed disodium-containing chemotherapy
• At least 4 weeks since prior major surgery
• At least 4 weeks since prior radiation therapy

• Measurable disease must be outside the radiation port
• Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) allowed

• Intrapleural cytotoxic chemotherapy will not be considered systemic chemotherapy
• At least 7 days since prior and no concurrent antithrombotic or anti-platelet agents, including any of the following:

• Aspirin or aspirin-containing combinations
• Clopidogrel
• Dipyridamole
• Tirofiban
• Epoprostenol
• Eptifibatide
• Cilostazol
• Abciximab
• Ticlopidine
• Warfarin

• Low-dose warfarin for prophylaxis to prevent catheter thrombosis allowed
• Heparin or low molecular weight heparin

• Heparin for IV line flush allowed
• At least 7 days since prior and no concurrent use of the following drugs:

• Itraconazole
• Ketoconazole (at doses > 200 mg/day)
• Miconazole
• Voriconazole
• Telithromycin
• Primidone
• Rifabutin
• Rifampin
• St. John's wort
• Carbamazepine
• Oxcarbazepine
• Rifapentine
• Phenobarbital
• Phenytoin
• Quinidine
• Procainamide
• Disopyramide
• Amiodarone
• Sotalol
• Ibutilide
• Dofetilide
• Erythromycin
• Clarithromycin
• Chlorpromazine
• Haloperidol
• Mesoridazine
• Thioridazine
• Pimozide
• Bepridil
• Droperidol
• Halofantrine
• Levomethadyl
• Sparfloxacin
• No concurrent H2 blockers or proton pump inhibitors
• No bisphosphonate therapy during the first 8 weeks of study treatment
• No concurrent hormones or other chemotherapeutic agents except for steroids administered for dasatinib-related pleural effusion or hormones administered for non-disease-related conditions (e.g., insulin for diabetes)
• No concurrent palliative radiation therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arkadiusz Dudek, MD

Role: STUDY_CHAIR

Masonic Cancer Center, University of Minnesota

Locations

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, United States

Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Elkhart General Hospital

Elkhart, Indiana, United States

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

Howard Community Hospital

Kokomo, Indiana, United States

Center for Cancer Therapy at LaPorte Hospital and Health Services

La Porte, Indiana, United States

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, United States

Memorial Hospital of South Bend

South Bend, Indiana, United States

Saint Joseph Regional Medical Center

South Bend, Indiana, United States

South Bend Clinic

South Bend, Indiana, United States

Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center

Baltimore, Maryland, United States

Union Hospital Cancer Program at Union Hospital

Elkton MD, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Lakeland Regional Cancer Care Center - St. Joseph

Saint Joseph, Michigan, United States

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Missouri Baptist Cancer Center

St Louis, Missouri, United States

Arch Medical Services, Incorporated at Center for Cancer Care and Research

St Louis, Missouri, United States

Methodist Estabrook Cancer Center

Omaha, Nebraska, United States

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, United States

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Wayne Memorial Hospital, Incorporated

Goldsboro, North Carolina, United States

Kinston Medical Specialists

Kinston, North Carolina, United States

Iredell Memorial Hospital

Statesville, North Carolina, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, United States

CCOP - Greenville

Greenville, South Carolina, United States

Mountainview Medical

Berlin Corners, Vermont, United States

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States

Danville Regional Medical Center

Danville, Virginia, United States

Countries

United States

References

Dudek A, Pang H, Kratzke RA, et al.: CALGB 30601: A phase II study of dasatinib (D) in patients (pts) with previously treated malignant mesothelioma (MM). [Abstract] J Clin Oncol 28 (Suppl 15) A-7037, 2010.

Reference Type: RESULT

Other Identifiers

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CALGB-30601

Identifier Type: -

Identifier Source: secondary_id

CDR0000558362

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-30601

Identifier Type: -

Identifier Source: org_study_id