Articles and Resources


Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2009
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00509041
  Purpose

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 Intervention Phase
Malignant Mesothelioma
Drug: dasatinib
Procedure: immunoenzyme technique
Procedure: immunohistochemistry staining method
Procedure: laboratory biomarker analysis
Phase II

MedlinePlus related topics: Cancer Mesothelioma
Drug Information available for: Dasatinib
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) at 24 weeks (or 5.5 months) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate (complete and partial response) as measured by RECIST criteria [ Designated as safety issue: No ]
  • Response duration [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Toxicity profile [ Designated as safety issue: Yes ]
  • Correlation of expression levels of EphA2 and PDGFRβ with response, PFS, and overall survival [ Designated as safety issue: No ]
  • Correlation of plasma levels of VEGF and PDGFRβ, serum levels of CSF-1, and soluble mesothelin-related protein with response, PFS, and overall survival [ Designated as safety issue: No ]
  • Correlation of a decrease in Src phosphorylation in PBMC with response, PFS, and overall survival [ Designated as safety issue: No ]
  • Correlation of a decrease in the phosphorylation of Src, EphA2, and PDGFRβ in tumor tissue with response [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: August 2007
Estimated Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
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 periodically.

Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  • Must 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
  • No prior tyrosine kinase, signal transduction, or angiogenesis inhibitor therapy
  • 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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00509041

Show 32 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Arkadiusz Dudek, MD Masonic Cancer Center, University of Minnesota
More Information


Study ID Numbers: CDR0000558362, CALGB-30601
Study First Received: July 30, 2007
Last Updated: January 15, 2009
ClinicalTrials.gov Identifier: NCT00509041  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
advanced malignant mesothelioma
epithelial mesothelioma
recurrent malignant mesothelioma
sarcomatous mesothelioma

Study placed in the following topic categories:
Dasatinib
Mesothelioma
Adenoma
Recurrence
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Neoplasms, Mesothelial
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 22, 2009

Source: www.ClinicalTrials.gov