AZD2171 in Treating Patients With Refractory Metastatic Kidney Cancer

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

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.

Study Overview

• Status: Terminated
• Conditions: Clear Cell Renal Cell Carcinoma; Stage IV Renal Cell Cancer; Recurrent Renal Cell Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: cediranib maleate

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.	Other: laboratory biomarker analysis; Correlative studies; Drug: cediranib maleate; Given orally; Other Names: AZD2171; Recentin

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: March 15, 2006
• First Submitted That Met QC Criteria: March 15, 2006
• First Posted (Estimate): March 17, 2006

Study Record Updates

• Last Update Posted (Estimate): May 21, 2014
• Last Update Submitted That Met QC Criteria: May 5, 2014
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Cediranib
• Other Study ID Numbers: NCI-2012-02686 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62201 (U.S. NIH Grant/Contract); P30CA014599 (U.S. NIH Grant/Contract); N01CM62209 (U.S. NIH Grant/Contract); CDR0000460237; UCCRC-NCI-7111; NCI-7111; 14018A (Other Identifier: University of Chicago); 7111 (Other Identifier: CTEP)