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

Advanced Adult Primary Liver Cancer Clinical Trial

Official title:

A Phase II Study of AZD2171 in Hepatocellular Carcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00427973
• Other study ID #: NCI-2009-00130
• Secondary ID: DFCI IRB 05-311N
• Status: Terminated
• Phase: Phase 2
• First received: January 25, 2007
• Last updated: March 13, 2013
• Start date: May 2009

Study information

• Verified date: March 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

• 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)

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• cediranib maleate
Given orally

Other:
• laboratory biomarker analysis

Procedure:
• computed tomography

• dynamic contrast-enhanced magnetic resonance imaging

Other:
• pharmacological study

Locations

Country	Name	City	State
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	This design yields at least 90% power to detect a true 3-month PFS rate of at least 69%.	3 months	No
Secondary	Response rate		Up to 1 year	No
Secondary	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.	The time from study entry until death from any cause, assessed up to 1 year	No