AZD2171 in Treating Patients With Refractory Metastatic Kidney Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00303862
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 60
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Cancer; Stage IV Renal Cell Cancer	Drug: cediranib maleate; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the objective response rate in patients with refractory metastatic renal cell carcinoma treated with AZD2171.

SECONDARY OBJECTIVES:

1. 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.

2. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 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 Patients With Advanced Renal Cell Carcinoma
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (cediranib maleate) 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; Given orally; Other Names: AZD2171 Recentin ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Objective Response [Up to 6 weeks]

   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

1. Performance of DCE_MRI [One month after initiating therapy]

   Binary (yes/no) indicator of whether a dynamic contrast-enhanced MRI (DCE-MRI)was successfully performed.

2. KDR [Day 28 after initiation of therapy]

   Kinase insert domain-containing vascular endothelial growth factor receptor

3. eNOS [Baseline (prior to therapy)]

   Endothelial nitric oxide synthase gene (eNOS). Record genotype=number of minor alleles.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Walter Stadler, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00303862
• Other Study ID Numbers: NCI-2012-02686; NCI-2012-02686; CDR0000460237; UCCRC-NCI-7111; NCI-7111; 14018A; 7111; P30CA014599; N01CM62201; N01CM62209
• First Posted: Mar 17, 2006
• Last Update Posted: May 21, 2014
• Last Verified: Jan 1, 2013

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

Study Results

Participant Flow

Recruitment Details	Patients were enrolled between December, 2006 and July, 2007 at three institutions. The trial was terminated after 10 patients were enrolled due to insufficent accrual rate.

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group Description	Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group Description	Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 60%
>=65 years	4 40%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.8 (11.0)
Sex: Female, Male (Count of Participants)
Female	3 30%
Male	7 70%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group Description	Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	20 200%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Because trial was closed due to poor accrual, MRI data were not collected.

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group Description	Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

3. Secondary Outcome

Title	KDR
Description	Kinase insert domain-containing vascular endothelial growth factor receptor
Time Frame	Day 28 after initiation of therapy

Outcome Measure Data

Analysis Population Description

Because trial was closed due to poor accrual, assays were not performed.

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group Description	Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

4. Secondary Outcome

Title	eNOS
Description	Endothelial nitric oxide synthase gene (eNOS). Record genotype=number of minor alleles.
Time Frame	Baseline (prior to therapy)

Outcome Measure Data

Analysis Population Description

Because trial was closed due to poor accrual, assays were not performed.

Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group Description	Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	Grade 2 or higher
Arm/Group Title	Treatment (Cediranib Maleate)
Arm/Group Description	Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Treatment (Cediranib Maleate)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Cediranib Maleate)
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Cediranib Maleate)
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Cardiac disorders
Hypertension	7/10 (70%)
Ear and labyrinth disorders
Ear, nose, and throat exam abnormal	2/10 (20%)
Endocrine disorders
Hyperglycemia	1/10 (10%)
Hyperthyroidism	1/10 (10%)
Hypothyroidism	3/10 (30%)
Gastrointestinal disorders
Abdominal pain	2/10 (20%)
Anorexia	1/10 (10%)
Diarrhea	4/10 (40%)
Flatulence	1/10 (10%)
Gastritis	1/10 (10%)
Nausea/vomiting	1/10 (10%)
General disorders
Fatigue	4/10 (40%)
Hand-and-foot syndrome	5/10 (50%)
Prostatic pain	1/10 (10%)
Infections and infestations
Infection	1/10 (10%)
Upper respiratory infection	1/10 (10%)
Metabolism and nutrition disorders
Alanine aminotransferase increased	1/10 (10%)
Alkaline phosphatase increased	1/10 (10%)
Creatinine increased	1/10 (10%)
Hypoalbuminemia	1/10 (10%)
Hypocalcemia	1/10 (10%)
Hypophophatemia	1/10 (10%)
Proteinuria	3/10 (30%)
Musculoskeletal and connective tissue disorders
Back pain	1/10 (10%)
Bone pain	1/10 (10%)
Muscle weakness	1/10 (10%)
Nervous system disorders
Neurological disorder NOS	1/10 (10%)
Seizure	1/10 (10%)
Psychiatric disorders
Anxiety	1/10 (10%)
Reproductive system and breast disorders
GU bleeding	1/10 (10%)
Urogenital disorder	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	1/10 (10%)
Respiratory disorder	1/10 (10%)

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.