Clinical Trial: Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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.

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.



Original Primary Outcome: Progression-free survival (PFS) at 24 weeks (or 5.5 months)

Current Secondary Outcome:

  • 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.


Original Secondary Outcome:

  • 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


Information By: Alliance for Clinical Trials in Oncology

Dates:
Date Received: July 30, 2007
Date Started: August 2007
Date Completion:
Last Updated: July 11, 2016
Last Verified: July 2016