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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00238394
First received: October 12, 2005
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Drug: cediranib maleate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of AZD2171 in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Survival after 6 months of treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Time to disease progression [ Time Frame: From registration to documentation of disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be estimated using the method of Kaplan-Meier.


Secondary Outcome Measures:
  • 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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Laboratory measures [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Descriptive statistics will be computed for the laboratory measures, including frequency and Cox proportional hazards modeling.


Enrollment: 44
Study Start Date: December 2005
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: cediranib maleate
Given orally
Other Names:
  • AZD2171
  • Recentin
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00238394

Locations
United States, Minnesota
North Central Cancer Treatment Group
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Alberts North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00238394     History of Changes
Other Study ID Numbers: NCI-2012-01822, N044J, CDR0000446081, NCCTG-N044J, U10CA025224
Study First Received: October 12, 2005
Last Updated: June 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014