eo-adjuvant dovitinib in patients with hepatocellular carcinoma prior to local treatment: a phase II study
- Conditions
- hepatocellular carcinomaliver cancer10019815
- Registration Number
- NL-OMON35941
- Lead Sponsor
- eids Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
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 x ULN
• Child-Pugh score of up to 6 points, i.e. Child-Pugh classe A (appendix 3), with no encephalopathy. Child-Pugh status must be calculated based on clinical findings and laboratory results during the baseline/screening period
• ALT and AST <= 3.0 x ULN (with or without liver metastases)
• Serum creatinine <= 1.5 x ULN or serum creatinine >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
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) <= 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
4. Patients who have received the last administration of nitrosurea or mitomycin-C <= 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
5. Patients who have received targeted therapy (e.g. sunitinib, sorafenib, pazopanib) <= 2 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
6. Patients who have had radiotherapy <= 4 weeks prior to starting study drug, or <= 2 weeks prior to starting study drug in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities
7. Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury <= 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device <= 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
8. Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
a. History or presence of serious uncontrolled ventricular arrhythmias
b. Clinically significant resting bradycardia
c. LVEF assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (which ever is higher) or multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (which ever is higher)
d. Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)
e. Uncontrolled hypertension defined by a SBP >= 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1. Toxicity and Safety of dovitinib (all grades, and grade 3 or 4 toxicities).<br /><br>2. Tumor response according to RECIST criteria (version 1.1) after 4 weeks of<br /><br>treatment as<br /><br>determined by CT-imaging and changes in intratumoral blood flow as measured by<br /><br>CT<br /><br>perfusion imaging.<br /><br>3. Histopathology of HCC specimens obtained following 4 weeks of treatment with<br /><br>dovitinib<br /><br>(comparison with pre-treatment biopsy, parameters: e.g. tumor necrosis,<br /><br>percentage of vital<br /><br>tumor cells, vascular density).</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Progression free survival of local relapse.<br /><br>2. Immunohistochemistry: changes in FGFR1, FGFR2, FGFR3, FGFR4, bFGF, FGF19,<br /><br>HGF,<br /><br>PLGF, cleaved caspase-3, Ki-67, CD31, pERK, M30/M65, and correlation with<br /><br>clinical data.<br /><br>3. Changes in plasma levels of VEGF, basic FGF, soluble VEGFR1, soluble VEGFR2,<br /><br>FGF2,<br /><br>FGF23, FGF19, HGF, cKit, and inhibition of ERK (extracellular receptor kinase)<br /><br>phosphorylation in PBMC*s (pre-treatment, day 15, day 26, and 1 month after<br /><br>local<br /><br>treatment) and correlation with clinical data.</p><br>