Clinical trial NCT00427973: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-01-29
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Progression-free Survival
timeFrame: 3 months
Secondary outcomes:
measure: Response Rate
timeFrame: Up to 1 year
measure: Overall Survival
timeFrame: The time from study entry until death from any cause, assessed up to 1 year
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Andrew Zhu
role: PRINCIPAL_INVESTIGATOR
References:
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.