S0509 - AZD2171 in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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This phase II trial is study how well AZD2171 works in treating patients with malignant pleural mesothelioma that cannot be removed by surgery. 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

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the objective confirmed, complete, and partial response rates in patients with unresectable malignant pleural mesothelioma treated with AZD2171. SECONDARY OBJECTIVES: I. Determine the clinical benefit, in terms of objective response and stable disease rates, in patients treated with this drug. II. Determine the 1-year median overall survival and progression-free survival in patients treated with this drug. III. Determine the frequency and severity of toxic effects in patients treated with this drug. IV. Correlate, preliminarily, pre- and post-treatment plasma vascular endothelial growth factor and soluble vascular cell adhesion molecule with clinical outcomes in patients treated with this drug. V. Correlate, preliminarily, circulating endothelial cells with clinical outcomes in patients treated with this drug. VI. Correlate variants of genes in the pathway targeted by this drug and variants of genes involved in the development of hypertension with the antiangiogenic property of this drug in these patients. OUTLINE: Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 5 years from study entry.

Official Title
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A Phase II Trial of Novel Oral Anti-Angiogenic Agent AZD2171 (NSC-732208) in Malignant Pleural Mesothelioma

Conditions
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Advanced Malignant Mesothelioma, Epithelial Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatous Mesothelioma

Intervention / Treatment
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* Drug: cediranib maleate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed epithelial, sarcomatous, or biphasic malignant pleural mesothelioma Unresectable disease Residual disease after prior cytoreductive surgery allowed Measurable disease by CT scan or MRI Prior treatment with platinum-based chemotherapy required No known CNS metastasis Performance status Zubrod 0-2 WBC >= 3,000/mm^3 Absolute neutrophil count >= 1,500/mm^3 Platelet count >= 100,000/mm^3 AST or ALT =< 1.5 times upper limit of normal (ULN) Bilirubin normal Creatinine =< 1.5 times ULN OR Creatinine clearance >= 50 mL/min Proteinuria =< 1+ by 2 consecutive dipstick tests taken >= 1 week apart No history of familial long QT syndrome Mean QTc =< 470 msec Systolic BP =< 150 mm Hg AND diastolic BP =< 100 mm Hg Must have New York Heart Association class I or II disease Class II must be controlled with treatment Able to swallow and/or receive enteral medications via gastrostomy feeding tube Not requiring IV alimentation No active peptic ulcer No intractable nausea or vomiting Not pregnant or nursing Fertile patients must use effective contraception No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in remission No history of hypersensitivity reaction to compounds of similar chemical or biological composition to the study drug Prior monoclonal antibody therapy targeting vascular endothelial growth factor (VEGF), VEGF receptor 1(VEGFR1) or VEGF receptor 2 (VEGFR2) allowed No other prior immunotherapy or biologic therapy No prior thymidine kinase inhibitor against VEGFR1 or VEGFR2 No concurrent drugs or biologics with proarrhythmic potential No more than 1 prior chemotherapy regimen At least 28 days since prior chemotherapy (42 days for nitrosoureas or mitomycin) and recovered At least 21 days since prior radiotherapy and recovered At least 28 days since prior major surgery (e.g., thoracotomy or laparotomy) and recovered No prior surgery that would affect absorption Stable antihypertensive therapy allowed provided blood pressure (BP) parameters are met Concurrent enrollment on SWOG-S9925 allowed No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (cediranib maleate)<br>Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: cediranib maleate<br>* Given orally<br>* Other names: Recentin;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | confirmed complete and partial responses per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.. | Disease assessments for response were performed every 8 weeks for as long as the patient remained on protocol treatment, up to 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | From the date of enrollment until the date of death due to any cause. Patients last known to be alive were censored at the date of last contact. | Daily during protocol treatment; then every 8 weeks until progression; then every 6 months for up to 3 years. | 
| Progression-free Survival | From the date of enrollment until the date of disease progression (as determined by standard RECIST), symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at the date of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Every 8 weeks until disease progression or death, up to 5 years. | 
| Disease Control Rate | The percentage of patients with a best of response of stable disease or better per standard RECIST. That is, patients whose best response was not increasing disease or death. | Every 8 weeks until disease progression progression, up to 5 years. | 
| Objective Response Rate Per Modified RECIST for Pleural Tumors | The sum of 6 pleural thickness measurements is added to sum of the longest diameters of all non-pleural measurable lesions. The resulting values are evaluated using RECIST. | Disease assessments for response were performed every 8 weeks as long as the patient remained on protocol treatment, up to 5 years. | 
| Adverse Event Rates | Adverse events per the NCI Common Toxicity Criteria version 3.0 that were possibly, probably or definitely related to protocol treatment. See adverse event tables for specific details. | Daily during protocol treatment | 
| Adverse Events | Only adverse events that are possibly, probably or definitely related to study drug are reported. | Patients were assessed for adverse events every day for as long as they remained on protocol treatment, up to 5 years. |