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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00227760
• Collaborator: (none)
• Enrollment: 44
• Locations: 6
• Arm: 1
• Duration (Months): 89
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer	Drug: Cediranib Maleate; Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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).

2. To assess the duration of response or stable disease, progression free, median and overall survival rates, and safety and tolerability of AZD2171.

3. 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.

4. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of AZD2171 in Progressive Unresectable, Recurrent or Metastatic Renal Cell Carcinoma (RCC)
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (cediranib maleate) Patients receive cediranib maleate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Cediranib Maleate; Given PO; Other Names: AZD2171 AZD2171 Maleate Recentin ; Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Correlative studies; Other Names: DCE MRI DCE-MRI DYNAMIC CONTRAST ENHANCED MRI ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Incidence of Durable Stable Disease, Evaluated Using the Response Evaluation Criteria in Solid Tumors (RECIST) [4 weeks]

   Stable disease for a clinical benefit rate, evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST)

2. Objective Response, Evaluated Using RECIST [4 weeks]

   Partial response as assessed by RECIST criteria

Secondary Outcome Measures

1. Progression Free Survival [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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
2	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
3	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
4	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
5	The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus	Ottawa	Ontario	Canada	K1Y 4E9
6	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Srikala Sridhar, University Health Network Princess Margaret Cancer Center P2C

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00227760
• Other Study ID Numbers: NCI-2013-01072; NCI-2013-01072; CDR0000446080; PHL-039; 7128; N01CM62203
• First Posted: Sep 28, 2005
• Last Update Posted: Feb 29, 2016
• Last Verified: Dec 1, 2013

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Recurrence; Cediranib; Maleic acid

Study Results

Participant Flow

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group 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. Cediranib Maleate: Given PO Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Period Title: Overall Study
STARTED	44
COMPLETED	44
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group 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. Cediranib Maleate: Given PO Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Participants	44
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	30 68.2%
>=65 years	14 31.8%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	9 20.5%
Male	35 79.5%
Region of Enrollment (participants) [Number]
Canada	44 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Evaluable patients

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group 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. Cediranib Maleate: Given PO Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	39
Number [particip[ants]	18

2. Primary Outcome

Title	Objective Response, Evaluated Using RECIST
Description	Partial response as assessed by RECIST criteria
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Evaluable patients

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group 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. Cediranib Maleate: Given PO Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	39
Number [participants]	15 34.1%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Total patients

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group 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. Cediranib Maleate: Given PO Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	44
Median (95% Confidence Interval) [months]	8.9

Adverse Events

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group 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. Cediranib Maleate: Given PO Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
All Cause Mortality
	Treatment (Cediranib Maleate)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Cediranib Maleate)
	Affected / at Risk (%)	# Events
Total	21/44 (47.7%)
Cardiac disorders
Myocardial infarction	2/44 (4.5%)	2
Chest pain - cardiac	2/44 (4.5%)	2
General disorders
Fatigue	1/44 (2.3%)	1
Musculoskeletal and connective tissue disorders
Chest wall pain	1/44 (2.3%)	1
Back pain	2/44 (4.5%)	2
Nervous system disorders
Syncope	1/44 (2.3%)	1
Seizure	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/44 (11.4%)	5
Hypoxia	1/44 (2.3%)	1
Vascular disorders
Thromboembolic event	1/44 (2.3%)	1
Vascular disorder - other	1/44 (2.3%)	1
Headache	3/44 (6.8%)	3
Other (Not Including Serious) Adverse Events
	Treatment (Cediranib Maleate)
	Affected / at Risk (%)	# Events
Total	2/44 (4.5%)
Infections and infestations
Infection and infestations - other	2/44 (4.5%)	2
Metabolism and nutrition disorders
Dehydration	2/44 (4.5%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.