AZD2171 in Treating Patients With Locally Advanced Unresectable or Metastatic Liver Cancer
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
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of AZD2171 in Hepatocellular Carcinoma|
- Progression-free Survival [ Time Frame: 3 months ] [ Designated as safety issue: No ]
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%.
- Response Rate [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
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
- Overall Survival [ Time Frame: The time from study entry until death from any cause, assessed up to 1 year ] [ Designated as safety issue: No ]Overall survival will be calculated using the Kaplan-Meier method, and confidence limits for survival estimates will be calculated using the Greenwood formula.
|Study Start Date:||May 2009|
|Study Completion Date:||March 2012|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
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
Other Name: AZD2171Other: 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-MRIOther: 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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00427973
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Andrew Zhu||Massachusetts General Hospital|