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


Phase 2
18 Years
N/A
Not Enrolling
Both
Malignant Mesothelioma

Thank you

Trial Information

A Phase II Study of Dasatinib (NSC #732517) in 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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

24 Week Progression Free Survival

Outcome Description:

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.

Outcome Time Frame:

24 weeks

Safety Issue:

No

Principal Investigator

Arkadiusz Dudek, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota

Authority:

United States: Federal Government

Study ID:

CDR0000558362

NCT ID:

NCT00509041

Start Date:

August 2007

Completion Date:

December 2012

Related Keywords:

  • Malignant Mesothelioma
  • advanced malignant mesothelioma
  • epithelial mesothelioma
  • recurrent malignant mesothelioma
  • sarcomatous mesothelioma
  • Mesothelioma

Name

Location

University of Chicago Cancer Research CenterChicago, Illinois  60637
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - GreenvilleGreenville, South Carolina  29615
CCOP - Northern Indiana CR ConsortiumSouth Bend, Indiana  46601
Saint Joseph Regional Medical CenterSouth Bend, Indiana  46617
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Wayne Memorial Hospital, IncorporatedGoldsboro, North Carolina  27534
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
Masonic Cancer Center at University of MinnesotaMinneapolis, Minnesota  55455
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Elkhart General HospitalElkhart, Indiana  46515
Howard Community HospitalKokomo, Indiana  46904
South Bend ClinicSouth Bend, Indiana  46617
Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital CenterBaltimore, Maryland  21237
Lakeland Regional Cancer Care Center - St. JosephSt. Joseph, Michigan  49085
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Fort Wayne Medical Oncology and HematologyFort Wayne, Indiana  46815
Center for Cancer Therapy at LaPorte Hospital and Health ServicesLa Porte, Indiana  46350
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Iredell Memorial HospitalStatesville, North Carolina  28677
Mountainview MedicalBerlin, Vermont  05602
Danville Regional Medical CenterDanville, Virginia  24541
Massachusetts General HospitalBoston, Massachusetts  02114-2617
Missouri Baptist Cancer CenterSt. Louis, Missouri  63131
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
Union Hospital Cancer Program at Union HospitalElkton MD, Maryland  21921
Arch Medical Services, Incorporated at Center for Cancer Care and ResearchSaint Louis, Missouri  63141
Kinston Medical SpecialistsKinston, North Carolina  28501