AZD2171 in Treating Patients With Locally Advanced Unresectable or Metastatic Liver Cancer
Condition: Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer
MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
Intervention: cediranib maleate; laboratory biomarker analysis; computed tomography; dynamic contrast-enhanced magnetic resonance imaging; pharmacological study
Intervention description: Given orally; 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.; computed tomography (CT) every 8 weeks to evaluate response and progression.; Magnetic resonance imaging (MRI) every 8 weeks to evaluate response and progression.; 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.
Intervention MeSH terms: Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

          -  AST and ALT =< 7 times upper limit of normal

          -  Creatinine =< 2.0 mg/dL

          -  Fertile patients must use effective contraception

          -  CLIP score =< 3

        Exclusion Criteria:

          -  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

          -  No other concurrent investigational agents

          -  No concurrent medication that may markedly affect renal function (e.g., vancomycin,
             amphotericin, or pentamidine)

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No other concurrent anticancer agents or therapies

          -  No mean QTc > 470 msec (with Bazett's correction) on screening EKG (490 msec for
             women)