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

Primary Purpose

Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

cediranib maleate

laboratory biomarker analysis

computed tomography

dynamic contrast-enhanced magnetic resonance imaging

pharmacological study

About this trial

This is an interventional treatment trial for Adult Primary Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Massachusetts General Hospital Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AZD2171

Arm Description

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.

Outcomes

Primary Outcome Measures

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%.

Secondary Outcome Measures

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

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.

Full Information

NCT ID

NCT00427973

First Posted

January 25, 2007

Last Updated

September 13, 2016

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00427973

Brief Title

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

Official Title

A Phase II Study of AZD2171 in Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Terminated

Why Stopped

The study was stopped prior to 2nd stage.

Study Start Date

May 2009 (undefined)

Primary Completion Date

April 2010 (Actual)

Study Completion Date

March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

Detailed Description

PRIMARY OBJECTIVE: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AZD2171

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

cediranib maleate

Other Intervention Name(s)

AZD2171

Intervention Description

Given orally

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

computed tomography

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

dynamic contrast-enhanced magnetic resonance imaging

Other Intervention Name(s)

DCE-MRI

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

pharmacological study

Other Intervention Name(s)

pharmacological studies

Intervention Description

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.

Primary Outcome Measure Information:

Title

Progression-free Survival

Description

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Response Rate

Description

Time Frame

Up to 1 year

Title

Overall Survival

Description

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

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andrew Zhu

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital Cancer Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

23362324

Citation

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.

Results Reference

result

Links:

URL

http://www.ncbi.nlm.nih.gov/pubmed/23362324

Description

pubmed article

Learn more about this trial

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

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