The primary objective of this study is to determine the efficacy of the combination of everolimus and capecitabine in a group of patients with metastatic or locally advanced HCC. In addition, to investigate biomarkers of HCC before and during the systemic treatment reflecting states of tumour cell growth and growth arrest (state of tumour cell dormancy). MedDRA version: 9.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable MedDRA version: 9.1 Level: LLT Clas
Conditions
Interventions
Trade Name: Xeloda
Product Name: Xeloda 500 mg and xeloda 150 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: EVEROLIMUS
CAS Number: 159351696
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
LUMC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Cytological or histological confirmed HCC who failed the standard therapies or who are not suitable for the standard therapies, i.e. metastectomy or liver transplantation. - Age > 18 years. - ECOG Performance Status of 0-2. - Life expectancy of at least 12 weeks. - Subjects with at least one uni-dimensional measurable lesion. Lesions must be measured by CT-scan or MRI. - Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: - Child-Pugh score of 7-9 points, i.e. Child-Pugh class B. - Total bilirubin 6 mmol/L. - Absolute neutrophil count (ANC) >1,500/mm3. - Platelet count ? 100,000/µl. - Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - History of cardiac disease: congestive heart failure >NYHA class 2; active coronary arterial disease (MI more than 6 mo prior to study entry is allowed); instable cardiac arrythmias; uncontrolled hypertension. - History of HIV infection. - Active clinically serious infections (> grade 2 NCI-CTC version 3.0) Hepatitis B carriers must be on lamivudine during and for 6 months after completion of study treatment. - Symptomatic metastatic brain or meningeal tumors - Patients with seizure disorder requiring medication (such as steroids or anti-epileptics). - Patients undergoing renal dialysis. - Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry. - Anticancer chemotherapy, immunotherapy, hormonal therapy, or radiotherapy during the study or within 4 weeks of study entry. Major surgery within 4 weeks of start of study. - Autologous bone marrow transplant or stem cell rescue within 4 months of study. - Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction]. Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study. - Investigational drug therapy outside of this trial during or within 4 weeks of study entry. - Prior exposure to the study drug. - Medical, psychological, or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results. - Patients unstable to swallow oral medications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Progression-free survival (PFS) at 6 months measured by CT-scan at 3-months intervals 2. Assessment of circulating levels of MP derived from vascular and/or tumour cells, and plasma MP-TF activity (prior to and during systemic treatment and following cessation of systemic treatment during progressive disease) 3. Circulating levels of biomarkers of the vasculature including endothelium activation marker such as VCAM, L-CAM, and P-selectin (prior to and during systemic treatment and following cessation of systemic treatment during progressive disease) 4. Investigation whether 2 and 3 are predictive factors for PFS and overall survival ;Secondary Objective: As secondary endpoints are defined: 1. Objective complete and partial response rate (RECIST criteria [appendix 1]/Waterfall plot) 2. Overall survival 3. One year survival rate 4. Safety 5. Alterations in cellular source of circulating MP during treatment as compared to pretreatment MP phenotype. 6. Assessment of development of venous thromboembolic events ;Primary end point(s): The primary objective of this study is to determine the efficacy of the combination of everolimus and capecitabine in a group of patients with metastatic or locally advanced HCC with Child-Pugh class B liver cirrosis. In addition, to investigate biomarkers of HCC before and during the systemic treatment reflecting states of tumour cell growth and growth arrest (state of tumour cell dormancy). Circulating proteins can be measured and used as reasonably reliable markers of changes in tumour cell load (e.g., alfa fertoprotein). 1. Progression-free survival (PFS) at 6 months measured by CT-scan at 3-months intervals 2. Assessment of circulating levels of MP derived from vascular and/or tumour cells, and plasma MP-TF activity (prior to and during systemic treatment and following cessation of systemic treatment during progressive disease) 3. Circulating levels of biomarkers of the vasculature including endotheliu | — |
Countries
Netherlands
Outcome results
None listed