Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology ( Cancer and Leukemia Group B )
ClinicalTrials.gov Identifier:
NCT00509041
First received: July 30, 2007
Last updated: April 29, 2013
Last verified: April 2013
  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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • 24 Week Progression Free Survival [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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:
  • Number of Participants With Overall Tumor Response [ Time Frame: Duration of study until progression (up to 3 years) ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 46
Study Start Date: August 2007
Study Completion Date: December 2012
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib
Use of dasatinib in treatment of pts with previously treated malignant mesothelioma
Drug: dasatinib
50 mg PO bid

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.

  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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00509041

  Show 37 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Arkadiusz Dudek, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
Publications:
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.

Responsible Party: Alliance for Clinical Trials in Oncology ( Cancer and Leukemia Group B )
ClinicalTrials.gov Identifier: NCT00509041     History of Changes
Other Study ID Numbers: CDR0000558362, U10CA031946, CALGB-30601
Study First Received: July 30, 2007
Results First Received: December 11, 2012
Last Updated: April 29, 2013
Health Authority: United States: Federal Government

Keywords provided by Alliance for Clinical Trials in Oncology:
advanced malignant mesothelioma
epithelial mesothelioma
recurrent malignant mesothelioma
sarcomatous mesothelioma

Additional relevant MeSH terms:
Lung Neoplasms
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Dasatinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014