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Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00509041
First received: July 30, 2007
Last updated: July 11, 2016
Last verified: July 2016
July 30, 2007
July 11, 2016
August 2007
February 2010   (Final data collection date for primary outcome measure)
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.
Progression-free survival (PFS) at 24 weeks (or 5.5 months)
Complete list of historical versions of study NCT00509041 on ClinicalTrials.gov Archive Site
  • 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.

  • 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.
  • 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.
  • Response rate (complete and partial response) as measured by RECIST criteria
  • Response duration
  • Overall Survival
  • Toxicity profile
  • Correlation of expression levels of EphA2 and PDGFRβ with response, PFS, and overall survival
  • Correlation of plasma levels of VEGF and PDGFRβ, serum levels of CSF-1, and soluble mesothelin-related protein with response, PFS, and overall survival
  • Correlation of a decrease in Src phosphorylation in PBMC with response, PFS, and overall survival
  • Correlation of a decrease in the phosphorylation of Src, EphA2, and PDGFRβ in tumor tissue with response
Not Provided
Not Provided
 
Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma
A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma

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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Malignant Mesothelioma
Drug: dasatinib
50 mg PO bid
Experimental: Dasatinib
Use of dasatinib in treatment of pts with previously treated malignant mesothelioma
Intervention: Drug: dasatinib
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
46
December 2012
February 2010   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00509041
CALGB-30601
U10CA031946 ( U.S. NIH Grant/Contract )
CALGB-30601
CDR0000558362 ( Registry Identifier: NCI Physician Data Query )
No
Not Provided
Not Provided
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Arkadiusz Dudek, MD Masonic Cancer Center, University of Minnesota
Alliance for Clinical Trials in Oncology
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP