AZD2171 in Treating Patients With Locally Advanced Unresectable or Metastatic Liver Cancer
NCT ID: NCT00427973
Last Updated: 2016-10-31
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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TERMINATED
PHASE2
17 participants
INTERVENTIONAL
2009-05-31
2012-03-31
Brief Summary
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Detailed Description
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I. Assess the progression free survival of patients with locally advanced unresectable or metastatic hepatocellular carcinoma treated with AZD2171.
SECONDARY OBJECTIVES:
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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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.
cediranib maleate
Given orally
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.
computed tomography
computed tomography (CT) every 8 weeks to evaluate response and progression.
dynamic contrast-enhanced magnetic resonance imaging
Magnetic resonance imaging (MRI) every 8 weeks to evaluate response and progression.
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.
Interventions
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cediranib maleate
Given orally
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.
computed tomography
computed tomography (CT) every 8 weeks to evaluate response and progression.
dynamic contrast-enhanced magnetic resonance imaging
Magnetic resonance imaging (MRI) every 8 weeks to evaluate response and progression.
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 Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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)
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Andrew Zhu
Role: PRINCIPAL_INVESTIGATOR
Massachusetts General Hospital
Locations
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Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Countries
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References
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Zhu AX, Ancukiewicz M, Supko JG, Sahani DV, Blaszkowsky LS, Meyerhardt JA, Abrams TA, McCleary NJ, Bhargava P, Muzikansky A, Sheehan S, Regan E, Vasudev E, Knowles M, Fuchs CS, Ryan DP, Jain RK, Duda DG. Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: a phase II study. Clin Cancer Res. 2013 Mar 15;19(6):1557-66. doi: 10.1158/1078-0432.CCR-12-3041. Epub 2013 Jan 29.
Related Links
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pubmed article
Other Identifiers
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05-311
Identifier Type: OTHER
Identifier Source: secondary_id
N02CO12400
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
CDR0000526405
Identifier Type: REGISTRY
Identifier Source: secondary_id
NCI-2009-00130
Identifier Type: -
Identifier Source: org_study_id