AZD2171 in Treating Patients With Refractory Metastatic Kidney Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well AZD2171 works in treating patients with refractory metastatic kidney cancer. 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 response rate in patients with refractory metastatic renal cell carcinoma treated with AZD2171. SECONDARY OBJECTIVES: I. Determine the safety and tolerability of AZD2171 in these patients. II. Determine the feasibility of performing standardized delayed contrast-enhancement-MRI correlative studies across different institutions and platforms with data-sharing capability in patients with metastatic renal cell cancer. III. Generate preliminary data regarding potential utility of pharmacogenomic and plasma/serum biomarkers of angiogenesis as predictive or prognostic markers for future investigations of AZD2171 and renal cell carcinoma. OUTLINE: This is a multicenter study. Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 6 weeks.

Official Title
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A Phase 2 Study of AZD2171 in Patients With Advanced Renal Cell Carcinoma

Conditions
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Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer

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 or cytologically confirmed clear cell renal cell cancer Must be predominantly metastatic disease Refractory disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mmby conventional techniques or ≥ 10 mm by spiral CT scan No known brain metastases ECOG performance status 0-2 Karnofsky 60-100% WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8.0 g/dL AST and ALT ≤ 2.5 times upper limit of normal (ULN) Bilirubin normal Creatinine normal OR creatinine clearance > 60 mL/min Blood pressure < 140/90 mm Hg on 2 separate occasions not more than 6 weeks prior to enrollment and not less than 24 hours apart (stable antihypertensive regimen allowed) Mean QTc ≤ 470 msec (with Bazett's correction) Less than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of familial long QT syndrome No cardiac arrhythmia No unstable angina pectoris No symptomatic congestive heart failure No New York Heart Association class III or IV disease No ongoing or active infection No hypertension No other uncontrolled intercurrent illness No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171 No psychiatric illness or social situations that would limit compliance with study requirements See Disease Characteristics More than 4 weeks since prior radiotherapy and recovered More than 4 weeks since prior major surgery and recovered More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered More than 30 days since other prior investigational agents No prior therapy with vascular endothelial growth factor (VEGF) binding agents or VEGF receptor (VEGFR) tyrosine kinase inhibitors No more than 1 prior nonVEGF-directed systemic therapy for this disease No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, ibuprofen, pentamidine) No combination antiretroviral therapy for HIV-positive patients No concurrent hematopoietic growth factors except epoetin alfa and bisphosphonates No concurrent hormones or other chemotherapeutic agents except for steroids given for adrenal failure and hormones administered for nondisease-related conditions (e.g. insulin for diabetes) No concurrent palliative or therapeutic radiation therapy No concurrent drugs or biologics with proarrhythmic potential No other concurrent investigational or commercial agents or therapies to treat the patient's malignancy

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 for 4 weeks. Treatment repeats every 4 weeks 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 |
| --- | --- | --- |
| Objective Response | Objective radiologic response as measured by RECIST criteria. (30% or greater shrinkage in the sum of the longest diameters of target lesions) | Up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance of DCE_MRI | Binary (yes/no) indicator of whether a dynamic contrast-enhanced MRI (DCE-MRI)was successfully performed. | One month after initiating therapy | 
| KDR | Kinase insert domain-containing vascular endothelial growth factor receptor | Day 28 after initiation of therapy | 
| eNOS | Endothelial nitric oxide synthase gene (eNOS). Record genotype=number of minor alleles. | Baseline (prior to therapy) |