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

Advanced Adult Primary Liver Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00238394
• Other study ID #: NCI-2012-01822
• Secondary ID: N044JCDR00004460
• Status: Completed
• Phase: Phase 2
• First received: October 12, 2005
• Last updated: June 4, 2013
• Start date: December 2005

Study information

• Verified date: June 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

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Intervention

Drug:
• cediranib maleate
Given orally

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	North Central Cancer Treatment Group	Rochester	Minnesota

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	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	No
Primary	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	No
Secondary	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	No
Secondary	Laboratory measures	Descriptive statistics will be computed for the laboratory measures, including frequency and Cox proportional hazards modeling.	Up to 5 years	No