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AZD2171 in Treating Patients With Refractory Metastatic Kidney Cancer

Primary Purpose

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

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cediranib maleate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clear Cell Renal Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cediranib maleate)

Arm Description

Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Objective Response
Objective radiologic response as measured by RECIST criteria. (30% or greater shrinkage in the sum of the longest diameters of target lesions)

Secondary Outcome Measures

Performance of DCE_MRI
Binary (yes/no) indicator of whether a dynamic contrast-enhanced MRI (DCE-MRI)was successfully performed.
KDR
Kinase insert domain-containing vascular endothelial growth factor receptor
eNOS
Endothelial nitric oxide synthase gene (eNOS). Record genotype=number of minor alleles.

Full Information

First Posted
March 15, 2006
Last Updated
May 5, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00303862
Brief Title
AZD2171 in Treating Patients With Refractory Metastatic Kidney Cancer
Official Title
A Phase 2 Study of AZD2171 in Patients With Advanced Renal Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Terminated
Study Start Date
March 2006 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cediranib maleate)
Arm Type
Experimental
Arm Description
Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
cediranib maleate
Other Intervention Name(s)
AZD2171, Recentin
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Objective Response
Description
Objective radiologic response as measured by RECIST criteria. (30% or greater shrinkage in the sum of the longest diameters of target lesions)
Time Frame
Up to 6 weeks
Secondary Outcome Measure Information:
Title
Performance of DCE_MRI
Description
Binary (yes/no) indicator of whether a dynamic contrast-enhanced MRI (DCE-MRI)was successfully performed.
Time Frame
One month after initiating therapy
Title
KDR
Description
Kinase insert domain-containing vascular endothelial growth factor receptor
Time Frame
Day 28 after initiation of therapy
Title
eNOS
Description
Endothelial nitric oxide synthase gene (eNOS). Record genotype=number of minor alleles.
Time Frame
Baseline (prior to therapy)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Walter Stadler
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

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AZD2171 in Treating Patients With Refractory Metastatic Kidney Cancer

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