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Adult Primary Hepatocellular CarcinomaPhase 2NCT00427973

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

A Phase 2 study testing cediranib maleate, laboratory biomarker analysis and computed tomography in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cediranib maleate, laboratory biomarker analysis and computed tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
May 2009to Mar 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: A Phase II Study of AZD2171 in Hepatocellular Carcinoma

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

Read the detailed description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

  1. 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.

Being tested
cediranib maleate, laboratory biomarker analysis, computed tomography, dynamic contrast-enhanced magnetic resonance imaging, pharmacological study
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cediranib maleateDrug

    Also called AZD2171

    Given orally

  • laboratory biomarker analysisOther

    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 tomographyProcedure or surgery

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

  • dynamic contrast-enhanced magnetic resonance imagingProcedure or surgery

    Also called DCE-MRI

    Magnetic resonance imaging (MRI) every 8 weeks to evaluate response and progression.

  • pharmacological studyOther

    Also called pharmacological studies

    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.

Study groups in NCT00427973
Study groupRoleWhat they receive
AZD2171ExperimentalPatients 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.
Receives: Drug: cediranib maleate; Other: laboratory biomarker analysis; Procedure: computed tomography; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival

    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%.

    Measured: 3 months

Secondary outcomes (2)

  1. Response Rate

    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

    Measured: Up to 1 year

  2. Overall Survival

    Overall survival will be calculated using the Kaplan-Meier method, and confidence limits for survival estimates will be calculated using the Greenwood formula.

    Measured: The time from study entry until death from any cause, assessed up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jan 2007 (estimated)
  2. Study startMay 2009
  3. Primary completionApr 2010
  4. Study completionMar 2012

Why it stopped: The study was stopped prior to 2nd stage.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00427973
Sponsor's protocol ID
NCI-2009-00130
Other IDs
05-311, N02CO12400, CDR0000526405
Status last verified
Sep 2016
First submitted
25 Jan 2007
Last updated
31 Oct 2016
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 23362324

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cediranib maleate, laboratory biomarker analysis and computed tomography in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00427973, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2016.

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