Multicentre, randomised, controlled, open-label, study comparing the efficacy and safety of slow repeated intravenous infusions of 2 doses of Doxorubicin Transdrug™ (DT) (20 mg/m² or 30 mg/m²) to those of best standard of care (BSC) in patients with advanced hepatocellular carcinoma (HCC) after failure or intolerance to sorafenib - ReLive Study - ReLive
- Conditions
- Advanced hepacellular carcinoma (HCC)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-002843-92-IT
- Lead Sponsor
- BioAlliance Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 397
1. Male or non-pregnant, non-breast feeding female;
2. Aged = 18 years;
3. Patients with
- advanced HCC (BCLC-C according to BCLC staging classification) having progressed under Sorafenib therapy or intolerant to Sorafenib, or
- intermediate HCC (BCLC-B) non eligible or non responders to transarterial chemoembolization (TACE), and having progressed under or intolerant to Sorafenib therapy;
4. Patients with porta hepatis lymph nodes, extrahepatic metastases, or portal/suprahepatic vein thrombosis without extension in inferior/superior vena cava, are eligible;
5. HCC diagnosed according to the AASLD and/or EASL criteria:
- Radiological Criteria applicable in cirrhotic liver:
- Nodule = 10 mm: one imaging technique among MRI and CT-scan showing typical appearances for HCC defined as arterial enhancement and rapid washout in portal venous or delayed phase;
- If appearance not typical for HCC on initial imaging: second contrast enhanced study (CT or MRI) showing typical appearances for HCC defined as arterial enhancement and rapid wash-out in portal venous or delayed phase;
- And/Or cyto-histology criteria (e.g. in case of atypical lesions for HCC at imaging, absence of cirrhosis);
6. Without cirrhosis or with a non decompensated cirrhosis (Child-Pugh score from A5 to B7 included);
7. ECOG Performance Status 0 or 1;
8. Adequate laboratory tests, in particular with:
- Platelets = 50,000 /mm3
- Neutrophil count = 1000 /mm3
- Hemoglobin = 10g/dL
- Serum transaminases < 5 ULN (NCI/CTC grades 0, 1, or 2)
- Alkaline phosphatases < 5 ULN (NCI/CTC grades 0, 1, or 2)
- Serum bilirubin < 35 µM/L (or 2.0 mg/dL);
9. Signed and dated written informed consent form.
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 97
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 118
1. Cirrhosis with a Child-Pugh score B8-C15;
2. Untreated chronic hepatitis B (in case of chronic hepatitis B, an efficacious antiviral treatment should have been started before randomisation to be included in the study);
3. Patients eligible for curative treatments (transplantation, surgical resection, percutaneous treatment);
4. Patients eligible for palliative treatments with demonstrated efficacy: TACE, Sorafenib; Patients who failed to Sorafenib treatment or intolerant to Sorafenib are eligible and can be included if Sorafenib has been stopped at least 2 weeks before randomization;
5. Prior history of malignancy with the exception of adequately treated basal cell carcinoma or in situ cervical cancer in complete remission since five years at least;
6. HCC developed on transplanted liver;
7. HIV infection;
8. Risk of variceal bleeding - i.e. patients with stage 2-3 varices with fragility signs (patients at risk for variceal bleeding may be included after a preventive treatment (oesophageal varices ligation, beta blockers)) has been administered; DT will not be administered in case of digestive bleeding in the 4 previous weeks;
9. SaO2 < 95%;
10. Presence of a significant acute or chronic respiratory disease defined as NCI /CTCAE > grade 2;
11. Presence of recent (< 6 months) or current cardiac failure (class III or IV NYHA classification), recent (< 6 months) acute coronary syndrome, clinically significant ECG abnormalities or recent (less than 6 months) acute vascular diseases (stroke, MI…);
12. Prior cumulative dose of 300 mg/m² of doxorubicin or equivalent;
13. Patients currently treated with immunosuppressive agents that cannot be stopped;
14. Patients whose medical or surgical conditions are unstable and may not allow the study completion or compliance, and specially patients with uncontrolled diabetes;
15. Uncontrolled systemic infection;
16. Patients with a life expectancy of less than 2 months;
17. Patients who have received an experimental drug in another clinical trial in the last 30 days prior to randomization in the present clinical trial;
18. Women of child-bearing age who are unwilling or unable to use an effective contraception method (oral contraception or intra-uterine device for woman) during the study treatment period and for 6 months after the last administration of study drug, and their male partner(s) refusing to use a condom (if applicable),
Men who are unwilling or unable to use a condom during the study treatment period and for 6 months after the last administration of study drug, and their female partner(s) refusing to use one of the appropriate effective contraception method (if applicable);
19. Patients unwilling or unable to comply with protocol requirements and scheduled visits.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the overall survival (OS) of repeated slow IV infusions of 20 or 30 mg/m2 DT to the Best Standard of Care (BSC) in patients with advanced HCC after failure or intolerance to Sorafenib.;Secondary Objective: - To compare additional efficacy parameters such as tumor response rate, progression free-survival (PFS) and time to progression (TTP) <br>- To determine the optimal dose of DT infusions;<br>- To evaluate the safety of DT;<br>- To assess PK parameters of DT at the doses of 20 and 30 mg/m2;<br>- To evaluate pharmacodynamics parameters and predictive factors of safety and efficacy: relationship between efficacy and safety (clinical, biological…) parameters, concentrations of doxorubicin and blood biomarkers.;Primary end point(s): Overall survival (OS);Timepoint(s) of evaluation of this end point: At each visit and until death
- Secondary Outcome Measures
Name Time Method