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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Adult Primary Hepatocellular Carcinoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: cediranib maleate

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • North Central Cancer Treatment Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (cediranib maleate); 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.

Other: laboratory biomarker analysis; Correlative studies; Drug: cediranib maleate; Given orally; Other Names: AZD2171; Recentin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: October 12, 2005
• First Submitted That Met QC Criteria: October 12, 2005
• First Posted (Estimate): October 13, 2005

Study Record Updates

• Last Update Posted (Estimate): June 5, 2013
• Last Update Submitted That Met QC Criteria: June 4, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Cediranib
• Other Study ID Numbers: NCI-2012-01822; U10CA025224 (U.S. NIH Grant/Contract); N044J; CDR0000446081; NCCTG-N044J