Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Active 18 and over NCI CALGB-30601 CALGB-30601, CALGB 30601, NCT00509041

Objectives

Primary

1. 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

1. To determine the response rate (partial response [PR] and complete response [CR]) in patients with malignant mesothelioma treated with dasatinib.
2. To determine the response duration in patients with malignant mesothelioma treated with dasatinib.
3. To describe the overall survival (OS) of patients with malignant mesothelioma treated with dasatinib.
4. To describe the toxicity profile of dasatinib in patients with malignant mesothelioma.
5. 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.
6. 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.
7. To determine whether inhibition of Src phosphorylation in PBMC correlates with PFS.
8. To assess inhibition of phosphorylation of Src, EphA2, and PDGFRβ in tumor tissue by dasatinib.

Entry 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

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

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)

Expected Enrollment

Outcomes

Progression-free survival (PFS) at 24 weeks (or 5.5 months)

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

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.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Arkadiusz Dudek, MD, Protocol chair		Ph: 612-624-6610; 888-226-2376 Email: dudek002@umn.edu

U.S.A.
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Clinical Trials Office - Tunnell Cancer Center	Ph:  302-645-3171
	Newark
	CCOP - Christiana Care Health Services
		Clinical Trial Office - CCOP - Christiana Care Health Services	Ph:  302-733-6227
District of Columbia
	Washington
	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
		Clinical Trials Office - Lombardi Comprehensive Cancer Center	Ph:  202-444-0381
Florida
	Orlando
	Florida Hospital Cancer Institute at Florida Hospital Orlando
		Clinical Trials Office - Florida Hospital Cancer Institute	Ph:  407-303-5623
Illinois
	Chicago
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
Indiana
	Fort Wayne
	Fort Wayne Medical Oncology and Hematology
		Sreenivasa Nattam, MD	Ph:  260-484-8830 800-852-2333
Maryland
	Baltimore
	Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
		Clinical Trials Office - Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Ph:  443-777-7364
	Elkton MD
	Union Hospital Cancer Program at Union Hospital
		Stephen Grubbs, MD	Ph:  410-398-4000
Minnesota
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Clinical Trials Office - Masonic Cancer Center at University of Minnesota	Ph:  612-624-2620
Missouri
	Saint Louis
	Arch Medical Services, Incorporated at Center for Cancer Care and Research
		Alan Lyss, MD	Ph:  314-628-1210
	Missouri Baptist Cancer Center
		Alan Lyss, MD	Ph:  314-996-5569 800-392-0936
Nebraska
	Omaha
	Methodist Estabrook Cancer Center
		Robert Langdon, MD	Ph:  402-354-5890 877-850-3212
New Jersey
	Voorhees
	Cancer Institute of New Jersey at Cooper - Voorhees
		Clinical Trials Office - Cancer Institute of New Jersey at Cooper University Hospital - Voorhees	Ph:  856-325-6757
New York
	Syracuse
	SUNY Upstate Medical University Hospital
		Clinical Trials Office - SUNY Upstate Medical University Hospital	Ph:  315-464-5476
North Carolina
	Goldsboro
	Wayne Memorial Hospital, Incorporated
		James Atkins, MD	Ph:  919-580-0000
	Kinston
	Kinston Medical Specialists
		Peter Watson, MD	Ph:  252-559-2200 ext. 201
Ohio
	Columbus
	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
		Clinical Trials Office - OSU Comprehensive Cancer Center	Ph:  614-293-4976
			Email: osu@emergingmed.com
Virginia
	Danville
	Danville Regional Medical Center
		Clinical Trials Office - Danville Regional Medical Center	Ph:  434-799-3753

Registry Information
Official Title		A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma
Trial Start Date		2007-08-15
Trial Completion Date		2008-07-17 (estimated)
Registered in ClinicalTrials.gov		NCT00509041
Date Submitted to PDQ		2007-06-26
Information Last Verified		2008-07-17
NCI Grant/Contract Number		CA31946

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