Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma

Malignant Mesothelioma Clinical Trial

Official title:

A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00509041
• Other study ID #: CDR0000558362
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 2
• First received: July 30, 2007
• Last updated: April 29, 2013
• Start date: August 2007
• Est. completion date: December 2012

Study information

• Verified date: April 2013
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: December 2012
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant mesothelioma of any of the following subtypes:

• Epithelial

• Sarcomatoid

• Mixed

• Any site of origin of malignant mesothelioma allowed including, but not limited to, any of the following:

• Pleura

• Peritoneum

• Pericardium

• Tunica vaginalis

• Pathology blocks or slides from a core surgical biopsy must be available

• Not amenable to curative surgery

• Measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as = 20 mm with conventional techniques (CT scan , MRI, or x-ray) or as = 10 mm with spiral CT scan

• Patients with pleural rind only disease must have at least one level with one rind measurement = 1.5 cm

• Lesions that are considered nonmeasurable include the following:

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Lymphangitis cutis/pulmonis

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• Prior treatment with one and only one systemic chemotherapy regimen, which must have included pemetrexed disodium required

• Treatment may have been with pemetrexed disodium alone or in combination with any other agent

• No symptomatic pleural effusions, unless the patient undergoes a therapeutic thoracentesis

• Patients with pleural effusions who have had a pleurodesis are eligible

• 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Neoplasms
• Malignant Mesothelioma
• Mesothelioma

Intervention

Drug:
• dasatinib
50 mg PO bid

Locations

Country	Name	City	State
United States	Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland
United States	Mountainview Medical	Berlin	Vermont
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital Cancer Program at Union Hospital	Elkton MD	Maryland
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Howard Community Hospital	Kokomo	Indiana
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
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	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Cancer and Leukemia Group B	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	24 Week Progression Free Survival	Percentage of participants who were alive and progression free at 24 weeks. The 24 week progression free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.	24 weeks	No
Secondary	Number of Participants With Overall Tumor Response	Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.; Overall tumor response is the total number of CR and PRs.	Duration of study until progression (up to 3 years)	No
Secondary	Overall Survival	Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.	Time from registration to death (up to 3 years)	No
Secondary	Progression Free Survival	Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.	Time from registration to progression or death (up to 3 years)	Yes