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AZD2171 in Treating Patients With Locally Advanced Unresectable or Metastatic Liver Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00427973
Recruitment Status : Terminated (The study was stopped prior to 2nd stage.)
First Posted : January 29, 2007
Results First Posted : October 31, 2016
Last Update Posted : October 31, 2016
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial is studying how well AZD2171 works in treating patients with locally advanced unresectable or metastatic liver 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
Adult Primary Hepatocellular Carcinoma Advanced Adult Primary Liver Cancer Localized Unresectable Adult Primary Liver Cancer Recurrent Adult Primary Liver Cancer Drug: cediranib maleate Other: laboratory biomarker analysis Procedure: computed tomography Procedure: dynamic contrast-enhanced magnetic resonance imaging Other: pharmacological study Phase 2

Detailed Description:


I. Assess the progression free survival of patients with locally advanced unresectable or metastatic hepatocellular carcinoma treated with AZD2171.


I. Determine the toxicity of this drug in these patients. II. Determine, preliminarily, the efficacy of this drug, in terms of response rate, duration of response, and overall survival, in these patients.

III. Determine the blood flow changes and vascular permeability of the tumor in patients treated with this drug.

IV. Determine the pharmacokinetic profile of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Dynamic contrast-enhanced (DCE) MRI and CT perfusion scan of the liver are performed at baseline, 72 hours after the initial dose of AZD2171, and at the end of course 1. Blood samples for pharmacokinetic studies are collected periodically during study.

After the completion of study treatment, patients are followed every 3 months for 1 year.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of AZD2171 in Hepatocellular Carcinoma
Study Start Date : May 2009
Actual Primary Completion Date : April 2010
Actual Study Completion Date : March 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arm Intervention/treatment
Experimental: AZD2171
Patients will receive AZD2171 (cediranib maleate) 30mg by mouth once a day. Treatment may continue for as long as benefit is shown. Patients will undergo MRI and CT scan of the liver before beginning treatment, 3 days after the first dose of AZD2171, and after finishing course one. Patients will also undergo blood collection periodically for laboratory studies. Laboratory biomarker analysis, computed tomography, dynamic contrast-enhanced magnetic resonance imaging, and pharmacological study will be performed.
Drug: cediranib maleate
Given orally
Other Name: AZD2171

Other: laboratory biomarker analysis
Peripheral blood was obtained from all patients enrolled for studies of early changes in circulating proangiogenic and proinflammatory molecules and cells. Blood samples were collected in EDTA-containing tubes before and after cediranib therapy on days 1 and 14 of cycle 1. Circulating VEGF, placental growth factor (PlGF), sVEGFR1, basic fibroblast growth factor (bFGF), interleukin (IL)-6, IL-8, transforming growth factor a ((TNF-a), gamma interferon (IFN-g) were measured using multiplex ELISA plates from Meso-Scale Discovery. Hepatocyte growth factor (HGF), insulin-like growth factor 1 (IGF-1), sVEGFR2, angiopoietin 2 (Ang-2), sTie2, soluble c-KIT, carbon anhydrase 9 (CAIX), and stromal cell-derived factor-1a (SDF1a) were measured using ELISA kits from R&D Systems.

Procedure: computed tomography
computed tomography (CT) every 8 weeks to evaluate response and progression.

Procedure: dynamic contrast-enhanced magnetic resonance imaging
Magnetic resonance imaging (MRI) every 8 weeks to evaluate response and progression.
Other Name: DCE-MRI

Other: pharmacological study
Blood samples to characterize the steady-state PK of cediranib were drawn from a peripheral vein shortly before patients received the dose on days 8 and 15 of cycle 1 and at the following times relative to dosing on day 1 of cycle 2: 5 min and 1, 2, 4, 6, 8, and 24 hours, with the last sample collected before taking the next daily dose.
Other Name: pharmacological studies

Primary Outcome Measures :
  1. Progression-free Survival [ Time Frame: 3 months ]

    Progression is defined as a 20% increase in the sum of the of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions by conventional RECIST based criteria, or death, which ever comes first.

    This design yields at least 90% power to detect a true 3-month PFS rate of at least 69%.

Secondary Outcome Measures :
  1. Response Rate [ Time Frame: Up to 1 year ]

    Number of patients who achieve either complete or partial response based on RECIST Criteria for target lesions assessed by MRI.

    Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  2. Overall Survival [ Time Frame: The time from study entry until death from any cause, assessed up to 1 year ]
    Overall survival will be calculated using the Kaplan-Meier method, and confidence limits for survival estimates will be calculated using the Greenwood formula.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically confirmed hepatocellular carcinoma
  • Locally advanced unresectable OR metastatic disease
  • Cancer of the Liver Italian Program (CLIP) score =< 3
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Measurable disease, defined as >= 1 unidimensionally measurable lesion>= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
  • Cardiac arrhythmia
  • Measurable lesion must be outside field of prior chemoembolization
  • No known brain metastases
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 12 weeks
  • Absolute neutrophil count >= 1,000/mm^3
  • Platelet count >= 75,000/mm^3
  • Hemoglobin >= 8 g/dL
  • Bilirubin =< 3.0 mg/dL
  • AST and ALT =< 7 times upper limit of normal
  • Creatinine =< 2.0 mg/dL
  • Fertile patients must use effective contraception
  • CLIP score =< 3

Exclusion Criteria:

  • Not pregnant or nursing
  • Negative pregnancy test
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD2171
  • No chronic diarrhea or any disorder that would limit adequate absorption of AZD2171
  • No familial history of long QT syndrome
  • Proteinuria =< +1 on two consecutive dipsticks taken no less than 1 week apart
  • No other uncontrolled illness including, but not limited to, any of the following:
  • Hypertension
  • Ongoing or active infection
  • No psychiatric illness or social situation that would limit study compliance
  • Recovered from prior therapy
  • Prior systemic chemotherapy regimens for hepatocellular carcinoma allowed
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • More than 4 weeks since prior radiotherapy, major surgery, or chemoembolization
  • At least 30 days since prior participation in an investigational trial
  • No other concurrent investigational agents
  • No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, or pentamidine)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer agents or therapies
  • No mean QTc > 470 msec (with Bazett's correction) on screening EKG (490 msec for women)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00427973

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United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Andrew Zhu Massachusetts General Hospital
Additional Information:
Publications of Results:
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00427973    
Other Study ID Numbers: NCI-2009-00130
05-311 ( Other Identifier: DFHCC IRB )
N02CO12400 ( Other Grant/Funding Number: US NIH Grant/Contract Award Number )
CDR0000526405 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 29, 2007    Key Record Dates
Results First Posted: October 31, 2016
Last Update Posted: October 31, 2016
Last Verified: September 2016
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors