AZD2171 in Treating Patients With Locally Advanced Unresectable or Metastatic Liver Cancer

NCT00427973 | Terminated Phase 2 Results DMC

• 4 other identifiers: NCI-2009-0013005-311N02CO12400CDR0000526405
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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

Conditions

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression is defined as a 20% increase in the sum of the of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions by conventional RECIST based criteria, or death, which ever comes first. This design yields at least 90% power to detect a true 3-month PFS rate of at least 69%.

  3 months

Secondary Outcomes (2)

• Response Rate

  Up to 1 year

• Overall Survival

  The time from study entry until death from any cause, assessed up to 1 year

Study Arms (1)

AZD2171

EXPERIMENTAL

Patients will receive AZD2171 (cediranib maleate) 30mg by mouth once a day. Treatment may continue for as long as benefit is shown. Patients will undergo MRI and CT scan of the liver before beginning treatment, 3 days after the first dose of AZD2171, and after finishing course one. Patients will also undergo blood collection periodically for laboratory studies. Laboratory biomarker analysis, computed tomography, dynamic contrast-enhanced magnetic resonance imaging, and pharmacological study will be performed.

Drug: cediranib maleate; Other: laboratory biomarker analysis; Procedure: computed tomography; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Other: pharmacological study

Interventions

cediranib maleate DRUG

Given orally

Also known as: AZD2171

AZD2171

laboratory biomarker analysis OTHER

Peripheral blood was obtained from all patients enrolled for studies of early changes in circulating proangiogenic and proinflammatory molecules and cells. Blood samples were collected in EDTA-containing tubes before and after cediranib therapy on days 1 and 14 of cycle 1. Circulating VEGF, placental growth factor (PlGF), sVEGFR1, basic fibroblast growth factor (bFGF), interleukin (IL)-6, IL-8, transforming growth factor a ((TNF-a), gamma interferon (IFN-g) were measured using multiplex ELISA plates from Meso-Scale Discovery. Hepatocyte growth factor (HGF), insulin-like growth factor 1 (IGF-1), sVEGFR2, angiopoietin 2 (Ang-2), sTie2, soluble c-KIT, carbon anhydrase 9 (CAIX), and stromal cell-derived factor-1a (SDF1a) were measured using ELISA kits from R\&D Systems.

AZD2171

computed tomography PROCEDURE

computed tomography (CT) every 8 weeks to evaluate response and progression.

AZD2171

dynamic contrast-enhanced magnetic resonance imaging PROCEDURE

Magnetic resonance imaging (MRI) every 8 weeks to evaluate response and progression.

Also known as: DCE-MRI

AZD2171

pharmacological study OTHER

Blood samples to characterize the steady-state PK of cediranib were drawn from a peripheral vein shortly before patients received the dose on days 8 and 15 of cycle 1 and at the following times relative to dosing on day 1 of cycle 2: 5 min and 1, 2, 4, 6, 8, and 24 hours, with the last sample collected before taking the next daily dose.

Also known as: pharmacological studies

AZD2171

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• 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.

  PMID: 23362324 RESULT

Related Links

• pubmed article

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

cediranib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Limitations and Caveats

Despite reaching the prespecified goal for the first stage of the trial, the study was stopped and did not proceed to the second stage after reviewing the development program of cediranib by AstraZeneca for reasons unrelated to this study.

Results Point of Contact

• Title: Andrew X. Zhu, MD
• Organization: Massachusetts General Hospital Cancer Center

azhu@partners.org

617-643-3415

Study Officials

• Andrew Zhu

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2007
• First Posted: January 29, 2007
• Study Start: May 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: March 1, 2012
• Last Updated: October 31, 2016
• Results First Posted: October 31, 2016

Record last verified: 2016-09

Locations

US (1)