A Phase II Study of AZD2171 in Hepatocellular Carcinoma
18 Years
N/A
Both
Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer
Trial Information
A Phase II Study of AZD2171 in Hepatocellular Carcinoma
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.
Inclusion Criteria
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)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression-free survival
Outcome Description:
This design yields at least 90% power to detect a true 3-month PFS rate of at least 69%.
Outcome Time Frame:
3 months
Safety Issue:
No
Principal Investigator
Andrew Zhu
Investigator Role:
Principal Investigator
Investigator Affiliation:
Massachusetts General Hospital
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00130
NCT ID:
NCT00427973
Start Date:
May 2009
Completion Date:
Related Keywords:
- Adult Primary Hepatocellular Carcinoma
- Advanced Adult Primary Liver Cancer
- Localized Unresectable Adult Primary Liver Cancer
- Recurrent Adult Primary Liver Cancer
- Carcinoma
- Liver Neoplasms
- Carcinoma, Hepatocellular
Name | Location |
|---|---|
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
