AZD2171 in Treating Patients With Refractory Metastatic Kidney Cancer

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00303862
First received: March 15, 2006
Last updated: May 5, 2014
Last verified: January 2013
  Purpose

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 Intervention Phase
Clear Cell Renal Cell Carcinoma
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Drug: cediranib maleate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AZD2171 in Patients With Advanced Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective Response [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: One month after initiating therapy ] [ Designated as safety issue: No ]
    Binary (yes/no) indicator of whether a dynamic contrast-enhanced MRI (DCE-MRI)was successfully performed.

  • KDR [ Time Frame: Day 28 after initiation of therapy ] [ Designated as safety issue: No ]
    Kinase insert domain-containing vascular endothelial growth factor receptor

  • eNOS [ Time Frame: Baseline (prior to therapy) ] [ Designated as safety issue: No ]
    Endothelial nitric oxide synthase gene (eNOS). Record genotype=number of minor alleles.


Enrollment: 10
Study Start Date: March 2006
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303862

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
Investigators
Principal Investigator: Walter Stadler University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00303862     History of Changes
Other Study ID Numbers: NCI-2012-02686, NCI-2012-02686, CDR0000460237, UCCRC-NCI-7111, NCI-7111, 14018A, 7111, P30CA014599, N01CM62201, N01CM62209
Study First Received: March 15, 2006
Results First Received: July 8, 2013
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014