hepatocellular carcinoma liver cancer
Conditions
Interventions
Patients will be treated with Dovitinib 500 mg/day orally during 5 days a week
for a total
period of 4 weeks, where after any form of local resection will be performed.
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histological or cytological confirmed HCC or HCC diagnosed by the Barcelona criteria. 2. HCC stage A or B according to the Barcelona Clinic Liver Cancer (BCLC) staging classification (appendix 2; Llovet et al, 2008a). 3. Patients eligible for local therapy, i.e. RF-ablation, chemo-embolization, or surgical resection 4. ECOG (WHO) performance status 0, 1, or 2 5. Age >= 18 years old 6. At least one uni-dimensional measurable lesion. Lesions must be measured by CT-scan or MRI-scan 7. Patients must have adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: • Absolute neutrophil count (ANC) >= 1.5 x 109/L • Platelets >= 75 x 109/L • Hemoglobin (Hgb) >= 6.0 mmol/L • Serum total bilirubin: 1.5 - 3 x ULN if calculated creatinine clearance (CrCl) is >= 30 mL/min using the Cockroft-Gault equation, see formula below: CrCl = [140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)] (if patient is female multiply the above by 0.85) 8. Life expectancy of at least 3 months 9. Patients who give a written informed consent obtained according to local guidelines
Exclusion criteria
Exclusion criteria: 1. Patients with brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases 2. Patients with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, skin cancer (such as basal cell carcinoma, squamous cell carcinoma, or non-melanomatous skin cancer), or superficial bladder tumors (Ta, Tis, and T1) 3. Patients who have received the last administration of an anticancer therapy including chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosurea, mitomycin-C, targeted therapy and radiation) = 160 mm Hg and/or DBP >= 100 mm Hg, with or without anti-hypertensive medication(s) • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) • Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Toxicity and Safety of dovitinib (all grades, and grade 3 or 4 toxicities). 2. Tumor response according to RECIST criteria (version 1.1) after 4 weeks of treatment as determined by CT-imaging and changes in intratumoral blood flow as measured by CT perfusion imaging. 3. Histopathology of HCC specimens obtained following 4 weeks of treatment with dovitinib (comparison with pre-treatment biopsy, parameters: e.g. tumor necrosis, percentage of vital tumor cells, vascular density). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Progression free survival of local relapse. 2. Immunohistochemistry: changes in FGFR1, FGFR2, FGFR3, FGFR4, bFGF, FGF19, HGF, PLGF, cleaved caspase-3, Ki-67, CD31, pERK, M30/M65, and correlation with clinical data. 3. Changes in plasma levels of VEGF, basic FGF, soluble VEGFR1, soluble VEGFR2, FGF2, FGF23, FGF19, HGF, cKit, and inhibition of ERK (extracellular receptor kinase) phosphorylation in PBMC*s (pre-treatment, day 15, day 26, and 1 month after local treatment) and correlation with clinical data. | — |
Countries
Netherlands
Outcome results
None listed