Clinical trial NCT00427973
Conditions: Adult Primary Hepatocellular Carcinoma Advanced Adult Primary Liver Cancer Localized Unresectable Adult Primary Liver Cancer Recurrent Adult Primary Liver Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2009-05-01; Completion date: 2012-03-01
Enrollment: 17 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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

Detailed description:
PRIMARY OBJECTIVE:

I. Assess the progression free survival of patients with locally advanced unresectable or metastatic hepatocellular carcinoma treated with AZD2171.

SECONDARY OBJECTIVES:

I. Determine the toxicity of this drug in these patients. II. Determine, preliminarily, the efficacy of this drug, in terms of response rate, duration of response, and overall survival, in these patients.

III. Determine the blood flow changes and vascular permeability of the tumor in patients treated with this drug.

IV. Determine the pharmacokinetic profile of this drug in these patients.

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. Dynamic contrast-enhanced (DCE) MRI and CT perfusion scan of the liver are performed at baseline, 72 hours after the initial dose of AZD2171, and at the end of course 1. Blood samples for pharmacokinetic studies are collected periodically during study.

After the completion of study treatment, patients are followed every 3 months for 1 year.

Arms: arm 1: 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.
Interventions: intervention 1: cediranib maleate intervention 2: laboratory biomarker analysis intervention 3: computed tomography intervention 4: dynamic contrast-enhanced magnetic resonance imaging intervention 5: pharmacological study
Intervention descriptions: intervention 1: Given orally intervention 2: 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. intervention 3: computed tomography (CT) every 8 weeks to evaluate response and progression. intervention 4: Magnetic resonance imaging (MRI) every 8 weeks to evaluate response and progression. intervention 5: 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.

Protocol documents: