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

Phase 2

Terminated

• Conditions: Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer
• Interventions: Drug: cediranib maleate; Other: laboratory biomarker analysis; Procedure: computed tomography; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Other: pharmacological study

• Registration Number: NCT00427973
• Lead Sponsor: National Cancer Institute (NCI)

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.

Study Timeline

• Study First Submitted: 2007-01-25
• Study First Submitted QC: 2007-01-25
• Study First Posted: 2007-01-29
• Study Start: 2009-05
• Primary Completion: 2010-04
• Study Completion: 2012-03
• Results First Submitted: 2015-07-01
• Status Verified: 2016-09
• Results First Submitted QC: 2016-09-13
• Last Update Submitted: 2016-09-13
• Results First Posted: 2016-10-31
• Last Update Posted: 2016-10-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 17

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AZD2171	cediranib maleate	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.
AZD2171	laboratory biomarker analysis	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.
AZD2171	computed tomography	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.
AZD2171	dynamic contrast-enhanced magnetic resonance imaging	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.
AZD2171	pharmacological study	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.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	3 months	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

Name	Time	Method
Response Rate	Up to 1 year	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	The time from study entry until death from any cause, assessed up to 1 year	Overall survival will be calculated using the Kaplan-Meier method, and confidence limits for survival estimates will be calculated using the Greenwood formula.

Trial Locations

Locations (1)

Massachusetts General Hospital Cancer Center; 🇺🇸 Boston, Massachusetts, United States