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Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00509041
Recruitment Status : Completed
First Posted : July 31, 2007
Results First Posted : January 17, 2013
Last Update Posted : August 11, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

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.


Condition or disease Intervention/treatment Phase
Malignant Mesothelioma Drug: dasatinib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma
Study Start Date : August 2007
Actual Primary Completion Date : February 2010
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma
Drug Information available for: Dasatinib

Arm Intervention/treatment
Experimental: Dasatinib
Use of dasatinib in treatment of pts with previously treated malignant mesothelioma
Drug: dasatinib
50 mg PO bid




Primary Outcome Measures :
  1. 24 Week Progression Free Survival [ Time Frame: 24 weeks ]
    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.


Secondary Outcome Measures :
  1. Number of Participants With Overall Tumor Response [ Time Frame: Duration of study until progression (up to 3 years) ]

    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.


  2. Overall Survival [ Time Frame: Time from registration to death (up to 3 years) ]
    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.

  3. Progression Free Survival [ Time Frame: Time from registration to progression or death (up to 3 years) ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00509041


Locations
Hide Hide 37 study locations
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United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Delaware
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
United States, Georgia
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
Savannah, Georgia, United States, 31403-3089
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Indiana
Elkhart General Hospital
Elkhart, Indiana, United States, 46515
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States, 46845
Howard Community Hospital
Kokomo, Indiana, United States, 46904
Center for Cancer Therapy at LaPorte Hospital and Health Services
La Porte, Indiana, United States, 46350
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
Memorial Hospital of South Bend
South Bend, Indiana, United States, 46601
Saint Joseph Regional Medical Center
South Bend, Indiana, United States, 46617
South Bend Clinic
South Bend, Indiana, United States, 46617
United States, Maryland
Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
Baltimore, Maryland, United States, 21237
Union Hospital Cancer Program at Union Hospital
Elkton MD, Maryland, United States, 21921
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Lakeland Regional Cancer Care Center - St. Joseph
St. Joseph, Michigan, United States, 49085
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Missouri Baptist Cancer Center
Saint Louis, Missouri, United States, 63131
Arch Medical Services, Incorporated at Center for Cancer Care and Research
Saint Louis, Missouri, United States, 63141
United States, Nebraska
Methodist Estabrook Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Jersey
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
United States, New York
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
Kinston Medical Specialists
Kinston, North Carolina, United States, 28501
Iredell Memorial Hospital
Statesville, North Carolina, United States, 28677
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210-1240
United States, South Carolina
CCOP - Greenville
Greenville, South Carolina, United States, 29615
United States, Vermont
Mountainview Medical
Berlin, Vermont, United States, 05602
Fletcher Allen Health Care - University Health Center Campus
Burlington, Vermont, United States, 05401
United States, Virginia
Danville Regional Medical Center
Danville, Virginia, United States, 24541
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Study Chair: Arkadiusz Dudek, MD Masonic Cancer Center, University of Minnesota

Publications of Results:
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.

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Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00509041    
Other Study ID Numbers: CALGB-30601
U10CA031946 ( U.S. NIH Grant/Contract )
CALGB-30601
CDR0000558362 ( Registry Identifier: NCI Physician Data Query )
First Posted: July 31, 2007    Key Record Dates
Results First Posted: January 17, 2013
Last Update Posted: August 11, 2016
Last Verified: July 2016
Keywords provided by Alliance for Clinical Trials in Oncology:
advanced malignant mesothelioma
epithelial mesothelioma
recurrent malignant mesothelioma
sarcomatous mesothelioma
Additional relevant MeSH terms:
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Mesothelioma
Lung Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action