Official Title: “Phase II Study of AZD2171 (NSC#732208) in Patients With Malignant Mesothelioma”

RATIONALE: AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well AZD2171 works in treating patients with malignant mesothelioma that cannot be removed by surgery.

Study Type: Interventional

Study Design: Treatment, Open Label

OBJECTIVES:

Primary - Determine the objective response rate in patients with malignant pleural, peritoneal, or tunica vaginalis mesothelioma that is not amenable to curative surgery who are treated with AZD2171.

Secondary - Determine the progression-free survival of patients treated with AZD2171. - Determine the toxicity experienced by patients treated with AZD2171. - Determine median and overall survival of patients treated with AZD2171.

Tertiary - Generate preliminary data regarding potential utility of pharmacogenomic and plasma/serum biomarkers of angiogenesis as predictive or prognostic markers for future investigations of this drug in malignant mesothelioma.

OUTLINE: This is a multicenter study.

Patients receive oral ADZ2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically during study for biomarker and optional pharmacogenomic correlative studies.

After completion of study treatment, patients are followed for up to 8 weeks.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant pleural, peritoneal, or tunica vaginalis mesothelioma
• Epithelial, sarcomatoid, or mixed subtype
• International Mesothelioma Interest Group stage II-IV disease (for patients with pleural mesothelioma)
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR > 10 mm by spiral CT scan
• Pleural effusion and ascites are not considered measurable lesions
• Disease not amenable to curative surgery
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100,000/mm³
• Total bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal (ULN)
• Creatinine normal OR creatinine clearance > 60 mL/min
• Fertile patients must use effective contraception
• Not pregnant or nursing
• Negative pregnancy test
• No history of allergic reactions to compounds of similar chemical or biologic composition to AZD2171
• Mean QTc ≤ 500 msec (with Bazett's correction) by EKG
• No history of long QT syndrome
• Proteinuria ≤ 1+ on two consecutive dipsticks taken ≥ 1 week apart
• No other concurrent malignancy
• No New York Heart Association class III or IV cardiac disease
• No uncontrolled intercurrent illness including, but not limited to, any of the following:
• Hypertension
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness or social situations that would limit study compliance

PRIOR CONCURRENT THERAPY:

• No more than 1 prior cytotoxic chemotherapy
• Prior intrapleural cytotoxic agents (including bleomycin) do not count towards prior cytotoxic chemotherapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• No prior radiotherapy to the only site of measurable disease
• At least 4 weeks since prior radiotherapy and recovered
• At least 4 weeks since prior major surgery and recovered
• More than 30 days since prior participation in an investigational trial
• No prior treatment with a vascular endothelial growth factor (VEGF) inhibitor
• No other concurrent investigational agents
• No concurrent commercial agents for the malignancy
• No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, or pentamidine)
• No concurrent hematopoietic growth factors except epoetin alfa
• No concurrent palliative radiotherapy
• No combination antiretroviral therapy for HIV-positive patients
• No concurrent drugs or biologics with proarrhythmic potential

Lead Sponsor: University of Chicago

City of Hope Comprehensive Cancer Center

Duarte California 91010-3000 United States

City of Hope Medical Group

Pasadena California 91105 United States

Contra Costa Regional Medical Center

Martinez California 94553 United States

Tower Cancer Research Foundation

Beverly Hills California 90211-1850 United States

University of California Davis Cancer Center

Sacramento California 95817 United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles California 90089-9181 United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood Illinois 60153 United States

Central Illinois Hematology Oncology Center

Springfield Illinois 62701 United States

Decatur Memorial Hospital Cancer Care Institute

Decatur Illinois 62526 United States

Evanston Northwestern Healthcare - Evanston Hospital

Evanston Illinois 60201-1781 United States

Ingalls Cancer Care Center at Ingalls Memorial Hospital

Harvey Illinois 60426 United States

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria Illinois 61615-7828 United States

University of Chicago Cancer Research Center

Chicago Illinois 60637-1470 United States

CCOP - Northern Indiana CR Consortium

South Bend Indiana 46601 United States

Fort Wayne Medical Oncology and Hematology

Fort Wayne Indiana 46885-5099 United States

Oncology Care Associates, PLLC

Saint Joseph Michigan 49085 United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey Pennsylvania 17033-0850 United States

Medical College of Wisconsin Cancer Center

Milwaukee Wisconsin 53226 United States

Princess Margaret Hospital

Toronto Ontario M5G 2M9 Canada

Overall Clinical Trial Officials and Contacts

Hedy L. Kindler, MD Principal Investigator University of Chicago  

Information obtained from ClinicalTrials.gov on July 23, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00309946

Study ID Number: CDR0000463521

ClinicalTrials.gov Identifier: NCT00309946

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database