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Cediranib Maleate in Treating Patients With Recurrent or Metastatic Kidney Cancer That Cannot Be Removed By Surgery

Primary Purpose

Recurrent Renal Cell Carcinoma, Stage IV Renal Cell Cancer

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Cediranib Maleate
Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Laboratory Biomarker Analysis
Pharmacological Study
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Renal Cell Carcinoma

Eligibility Criteria

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

Inclusion Criteria: Patients must have histologically or cytologically confirmed renal cell cancer that is locally recurrent or metastatic and is not considered curable by standard therapy Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan; bone lesions are not considered to be measurable; all radiology must be performed within 28 days prior to registration Previous therapy: Surgery: Previous surgery is permissible; patients must be >= 4 weeks since any major surgery Chemotherapy: No previous systemic chemotherapy Immunotherapy: No previous therapy permitted Gene/investigational therapy: No prior therapy is permitted Radiation: Patients may have had radiation therapy but must have recovered from acute toxic effects prior to registration; at least 4 weeks must have elapsed since last dose of radiation before registration (exceptions may be made for low-dose, non-myelosuppressive radiotherapy); if the sole site of measurable disease is in a radiation field, there must have been documented progression at that site for patient to be eligible Life expectancy of greater than 3 months Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) Absolute neutrophil count >= 1.5 x10^9/L Platelets >= 100 x10^9/L Total bilirubin =< 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 × institutional ULN Creatinine =< 1.5 x ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on vascular endothelial growth factor (VEGF) signaling; for this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had radiotherapy, or major surgery within 4 weeks prior to entering the study or those who have not recovered from adverse events of these therapies Patients may not be receiving any other investigational agents nor have participated in an investigational trial Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171 Mean corrected QT interval (QTc) > 470 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because AZD2171 is a VEGF inhibitor with known abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD2171, breastfeeding should be discontinued if the mother is treated with AZD2171 Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated Any significant abnormality noted in the electrocardiogram (ECG) within 14 days of treatment A New York Heart Association classification of III or IV (NOTE: Patients classified as class II controlled with treatment may continue with increase monitoring) Conditions requiring concurrent use of drugs or biologics with proarrhythmic potential; these drugs are prohibited during studies with AZD2171

Sites / Locations

  • Cross Cancer Institute
  • BCCA-Vancouver Cancer Centre
  • Juravinski Cancer Centre at Hamilton Health Sciences
  • London Regional Cancer Program
  • The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
  • University Health Network-Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cediranib maleate)

Arm Description

Patients receive cediranib maleate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Incidence of Durable Stable Disease, Evaluated Using the Response Evaluation Criteria in Solid Tumors (RECIST)
Stable disease for a clinical benefit rate, evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST)
Objective Response, Evaluated Using RECIST
Partial response as assessed by RECIST criteria

Secondary Outcome Measures

Progression Free Survival

Full Information

First Posted
September 26, 2005
Last Updated
January 29, 2016
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00227760
Brief Title
Cediranib Maleate in Treating Patients With Recurrent or Metastatic Kidney Cancer That Cannot Be Removed By Surgery
Official Title
A Phase 2 Study of AZD2171 in Progressive Unresectable, Recurrent or Metastatic Renal Cell Carcinoma (RCC)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (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 studies how well cediranib maleate works in treating patients with recurrent or metastatic kidney cancer that cannot be removed by surgery. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the clinical benefit rate (objective response rate and rate of stable disease for at least 4 months) of AZD2171 (cediranib maleate) given to patients with progressive unresectable or, recurrent or metastatic renal cell carcinoma (RCC). II. To assess the duration of response or stable disease, progression free, median and overall survival rates, and safety and tolerability of AZD2171. III. To measure baseline and post treatment levels of soluble markers of angiogenic growth factors and receptors as well as levels of circulating endothelial cells, and correlate these with clinical outcome. IV. To assess changes in blood flow and vessel permeability using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) pre and post treatment and to correlate these changes with clinical outcome. OUTLINE: Patients receive cediranib maleate orally (PO) once daily (QD) 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 up at 4 weeks and then every 3 months thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Renal Cell Carcinoma, 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
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cediranib maleate)
Arm Type
Experimental
Arm Description
Patients receive cediranib maleate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Cediranib Maleate
Other Intervention Name(s)
AZD2171, AZD2171 Maleate, Recentin
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Other Intervention Name(s)
DCE MRI, DCE-MRI, DYNAMIC CONTRAST ENHANCED MRI
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Incidence of Durable Stable Disease, Evaluated Using the Response Evaluation Criteria in Solid Tumors (RECIST)
Description
Stable disease for a clinical benefit rate, evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame
4 weeks
Title
Objective Response, Evaluated Using RECIST
Description
Partial response as assessed by RECIST criteria
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Progression Free Survival
Time Frame
Time from start of treatment to progression, death or last contact, or last tumor assessment before the start of further antitumor therapy, assessed up to 6.5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically confirmed renal cell cancer that is locally recurrent or metastatic and is not considered curable by standard therapy Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan; bone lesions are not considered to be measurable; all radiology must be performed within 28 days prior to registration Previous therapy: Surgery: Previous surgery is permissible; patients must be >= 4 weeks since any major surgery Chemotherapy: No previous systemic chemotherapy Immunotherapy: No previous therapy permitted Gene/investigational therapy: No prior therapy is permitted Radiation: Patients may have had radiation therapy but must have recovered from acute toxic effects prior to registration; at least 4 weeks must have elapsed since last dose of radiation before registration (exceptions may be made for low-dose, non-myelosuppressive radiotherapy); if the sole site of measurable disease is in a radiation field, there must have been documented progression at that site for patient to be eligible Life expectancy of greater than 3 months Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) Absolute neutrophil count >= 1.5 x10^9/L Platelets >= 100 x10^9/L Total bilirubin =< 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 × institutional ULN Creatinine =< 1.5 x ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on vascular endothelial growth factor (VEGF) signaling; for this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had radiotherapy, or major surgery within 4 weeks prior to entering the study or those who have not recovered from adverse events of these therapies Patients may not be receiving any other investigational agents nor have participated in an investigational trial Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171 Mean corrected QT interval (QTc) > 470 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because AZD2171 is a VEGF inhibitor with known abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD2171, breastfeeding should be discontinued if the mother is treated with AZD2171 Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated Any significant abnormality noted in the electrocardiogram (ECG) within 14 days of treatment A New York Heart Association classification of III or IV (NOTE: Patients classified as class II controlled with treatment may continue with increase monitoring) Conditions requiring concurrent use of drugs or biologics with proarrhythmic potential; these drugs are prohibited during studies with AZD2171
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Srikala Sridhar
Organizational Affiliation
University Health Network Princess Margaret Cancer Center P2C
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
BCCA-Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Juravinski Cancer Centre at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
London Regional Cancer Program
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
University Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

Cediranib Maleate in Treating Patients With Recurrent or Metastatic Kidney Cancer That Cannot Be Removed By Surgery

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