advanced hepatocellular carcinoma MedDRA version: 21.0 Level: LLT Classification code 10024662 Term: Liver cell carcinoma non-resectable System Organ Class: 100000004864
Conditions
Interventions
Trade Name: XELODA - 500 MG 120 COMPRESSE FILMRIVESTITE IN BLISTER USO ORALE
Product Name: xeloda
Product Code: [xeloda]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: CAPECITABINA
Curre
Sponsors
AOU DI BOLOGNA POLICLINICO S.ORSOLA-MALPIGHI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The patient has provided signed informed consent and is amenable to compliance with protocol schedules and testing; 2. The patient is at last 18 years of age whichever is older; 3. Eastern Cooperative Oncology Group performance status =2; 4. The patient has advanced HCC, with BCLC stage C at the randomization. A patient with BCLC stage B may be eligible if he/she has disease that is not amenable or refractory to locoregional therapy (examples include very large or diffusely infiltrative tumors and intrahepatic tumors refractory or not amenable to locoregional treatment); 5. Histological confirmation of diagnosis isn’t mandatory, provided that American Association for the Study of Liver Diseases diagnostic criteria AASLD criteria (22) is fulfilled; 6. Presence of at least one measurable lesion in accordance to the modified Response Evaluation Criteria in Solid Tumors (mRECIST); not previously treated with locoregional therapy. A lesion that has been previously treated will qualify as a measurable or evaluable lesion if there was demonstrable progression following locoregional therapy; 7. Adequate hepatic function (CP-A); 8. Life expectancy of at least three months; 9. Adequate haematological (Hb=8.5 g/dl, neutrophils =1000/µl, platelets =60000/µl), hepatic (total bilirubin = 3.0 mg/dl; ALT and AST = 5 x ULN; INR = 2.3 or PTT = 6 second above ULN) and renal functions (serum creatinine = 1.5 x ULN); 10. Concomitant antiviral therapy against HBV is required according to local guidelines; 11. Resolution of all acute toxic effect of any prior local treatment to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03) (NCICTCAE v 4.03) grade = 1. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 158
Exclusion criteria
Exclusion criteria: 1. Previous systemic treatment for HCC; 2. Fibrolamellar HCC, mixed hepatocellular cholangiocarcinoma or HCC relapsed after orthotopic liver transplantation 3. Patients putatively eligible for treatment with Regorafenib after progression with sorafenib in the absence of toxicity; 4. The patient has undergone surgery or hepatic locoregional therapy within 28 days prior to randomization; 5. History of hypersensitivity to fluorouracil; 6. Know Dihydropyrimidine dehydrogenase (DPD) deficiency; 7. Ongoing cardiac dysrhythmias of NCI CTAE 8. Treatment with potent CYP3A4 9. Concomitant treatment with botanical formulation having an approved indication for cancer treatment, 10. The patient is pregnant 11. Pts affect by medical or social problems potentially impairing compliance to the study protocol; 12. Presence of F3 varices untreatable with beta-blocker therapy with patient's refusal to undergo prophylactic band ligation treatment. Digestive bleeding due to ruptured varices in the last two months; 13. Presence of clinically relevant ascites (e.g. requiring therapeutic paracentesis or that can be classified as Child- Pugh >2);
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Increase in patient OS at 1 year of treatment of 15% or 1.34 times (relative risk) with Capecitabine first-line (arm A) compared to Sorafenib first-line (arm B).;Secondary Objective: •Relative increase in PFS (PFS) at 1 year of treatment of at least 1.2 times with Capecitabine compared to Sorafenib; •Reduction of drug-related direct costs at 1 year of 50% in arm A; •Better quality of life during treatment with Capecitabine compared to Sorafenib; •Improved cost-effectiveness correlated to quality of life with Capecitabine compared to Sorafenib of 50% at 1 year of treatment; •Explorative analysis of time to failure strategy (TFS) that is the sum of first and second-line PFS and of the time elapsed between the failure of the first-line and the beginning of the second-line; • An ancillary objective will be the evaluation of CECs, CEPs and angiogenesis markers in the enrolled population to identify putative biomarkers of PFS and the efficacy of metronomic treatment, both in first and second-line (See Sub-study Protocol- Section 5);Primary end point(s): •Increase in patient OS at 1 year of treatment of 15% or 1.34 times (relative risk) with Capecitabine first-line (arm A) compared to Sorafenib first-line (arm B);Timepoint(s) of evaluation of this end point: 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Relative increase in PFS (PFS) at 1 year of treatment of at least 1.2 times with Capecitabine compared to Sorafenib; • Reduction of drug-related direct costs at 1 year of 50% in arm A; • Better quality of life during treatment with Capecitabine compared to Sorafenib; • Improved cost-effectiveness correlated to quality of life with Capecitabine compared to Sorafenib of 50% at 1 year of treatment; • Explorative analysis of time to failure strategy (TFS) that is the sum of first and second-line PFS and of the time elapsed between the failure of the first-line and the beginning of the second-line; • An ancillary objective will be the evaluation of CECs, CEPs and angiogenesis markers in the enrolled population to identify putative biomarkers of PFS and the efficacy of metronomic treatment, both in first and second-line (See Sub-study Protocol- Section 5);Timepoint(s) of evaluation of this end point: 18 months | — |
Countries
Italy
Contacts
Public ContactU.O. Medicina per la Continuità Ass
AOU di Bologna Policlinico S.Orsola-Malpighi
Outcome results
None listed