Cediranib Maleate in Treating Patients With Locally Advanced or Metastatic Liver Cancer

Study Overview
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Brief Summary
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AZD2171 (cediranib maleate) 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. This phase II trial is studying how well AZD2171 works in treating patients with locally advanced or metastatic liver cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the 6-month survival of patients with locally advanced or metastatic hepatocellular carcinoma treated with AZD2171. SECONDARY OBJECTIVES I. Determine tumor response and time to progression in patients treated with this drug. II. Determine the toxicity of this drug in these patients. III. Correlate biological markers with response in patients treated with this drug. 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. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. Patients experiencing disease progression within 5 years after completion of study treatment may receive additional courses of study treatment. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 4 years. PROJECTED ACCRUAL: A total of 20-44 patients will be accrued for this study within 22 months.

Official Title
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A Phase II Study of AZD2171 in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma

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

Intervention / Treatment
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* Drug: cediranib maleate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed hepatocellular carcinoma Locally advanced or metastatic disease Not amenable to treatment with surgery or orthotopic liver transplantation Measurable or non-measurable disease Measurable disease is defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Evidence of disease progression by imaging on serial exams or biochemical evidence of a rising alpha fetoprotein on serial testing No history of brain metastases other than locally treatable CNS lesions (i.e., lesions treatable with surgery or radiosurgery) Patients with locally treatable CNS disease eligible provided they were previously treated and had no evidence of CNS progression for ≥ 4 weeks after completion of treatment No fibrolamellar hepatocellular carcinoma or mixed cholangiocarcinoma/hepatocellular carcinoma Performance status - ECOG 0-1 Absolute neutrophil count ≥ 1,200/mm^3 Platelet count ≥ 75,000/mm^3 Hemoglobin ≥ 10.0 g/dL Bilirubin ≤ 3 times upper limit of normal (ULN) AST ≤ 5 times ULN Alkaline phosphatase ≤ 5 times ULN Urine protein < 1+ by urine dip stick OR proteinuria < 1 gm/24-hour collection QTc prolongation ≤ 500 msec No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled blood pressure, defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg No significant ECG abnormality within the past 14 days No New York Heart Association class III or IV disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No history of allergic reaction to compounds of similar chemical or biological composition to AZD2171 No ongoing or active infection No psychiatric illness or social situation that would preclude study participation No other uncontrolled illness More than 4 weeks since prior biologic therapy More than 4 weeks since prior and no concurrent immunotherapy No colony-stimulating factors during the first course of study treatment At least 6 weeks since prior chemoembolization Patients must have evidence of disease progression or new metastases after prior chemoembolization No prior systemic chemotherapy for this cancer No other concurrent chemotherapy More than 4 weeks since prior hormonal therapy See Disease Characteristics At least 6 weeks since prior radiofrequency ablation or other local ablative therapy Patients must have evidence of disease progression or new metastases after prior radiofrequency ablation or other local ablative therapy No prior external beam radiotherapy to the primary site No prior radiotherapy to ≥ 25% of the bone marrow No concurrent radiotherapy See Disease Characteristics No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent drugs or biologics with proarrhythmic potential

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (cediranib maleate)<br>Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive 2 additional courses beyond CR. Patients experiencing disease progression within 5 years after completion of study treatment may receive additional courses of study treatment. | Drug: cediranib maleate<br>* Given orally<br>* Other names: Recentin;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival after 6 months of treatment | Will be estimated by the proportion of patients surviving more than 6 months. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. | 6 months | 
| Time to disease progression | Will be estimated using the method of Kaplan-Meier. | From registration to documentation of disease progression, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed tumor response is defined to be a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart |  | Up to 5 years | 
| Laboratory measures | Descriptive statistics will be computed for the laboratory measures, including frequency and Cox proportional hazards modeling. | Up to 5 years |