Second-line treatment for adult patient with unresectable advanced or metastatic hepatocellular cancer. MedDRA version: 14.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: Ro 513-7382/F02
Pharmaceutical Form: Solution for infusion
Current Sponsor code: RO5137382
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400 mg-
Pha
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female =18 years old 2. Life expectancy of at least 12 weeks 3. ECOG Performance Status of 0 or 1 4. Histologically confirmed unresectable advanced or metastatic hepatocellular carcinoma (without fibrolamellar subtype) patients who are not candidate for or progressed on loco-regional therapy 5. Prior treatment with at least 1 systemic agent, (such as Sorafenib or other experimental agents), with documented progressive disease after systemic agent(s), or documented adverse event(s) associated with prior systemic agent(s) that resulted in discontinuance of that(those) agent(s) 6. Not a candidate for curative treatments (e.g. resection, transplantation) 7. Child-Pugh A ( score of 5-6) 8. Adequate hematologic function: Platelet count = 50x 109/L, Absolute Neutrophil Count = 1,500/µL, Hemoglobin = 8.0 g /dL 9. Adequate hepatic function: ALT (SGPT), AST (SGOT) = 5 x ULN, Bilirubin = 2 mg/ dL 10. Adequate renal function: Serum Creatinine = 2 x ULN or calculated Creatinine Clearance = 60 ml/min using Cockcroft and Gault formula 11. Ability to provide, for central review, a tumor tissue sample containing at least 5 % tumor cells to determine the level of GPC-3 expression by IHC. Determination of GPC-3 expression level is required prior to study entry. 12. Patients must have recovered from effects of any major surgery or significant traumatic injury at least 14 days before the first dose of study treatment 13. Measurable disease (by RECIST 1.1) prior to the administration of study treatment 14. Negative serum pregnancy test 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 85 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 86
Exclusion criteria
Exclusion criteria: 1. Child-Pugh B or C 2. Known HCC with fibro-lamellar histology 3. Known brain or leptomeningeal metastases 4. Patients with a previous malignancy within the past 5 years are excluded(patients who had curatively treated basal cell carcinoma of the skin,early gastrointestinal cancer by endoscopic resection, and/or insitu carcinoma of the cervix and other malignancies which were considered cured and deemed by the PI to have no impact on the PFS and OS are allowed after discussion with the study medical monitor) 5. Active infectious diseases requiring treatment except for hepatitis B and C 6. NCI CTCAE version 4.0 grade 3 hemorrhage within 4 weeks of starting the study treatment 7. History of organ allograft including liver transplant 8. Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study 9. Patient who have had any anticancer treatment within 2 weeks prior to entering the study 10. Patients who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies 11. Patients receiving Interferon therapy 12. Patients with baseline QTc > 470 ms, or patients with baseline resting bradycardia <45 beats per minutes. 13. Patients who received anticoagulation or thrombolytic agents for therapeutic purposes (except for low-dose administration for catheter clearance or for prophylactic purposes) within 2 weeks prior to Day 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy of GC33 vs. placebo through investigator-assessed progression-free survival (PFS) in patients with unresectable advanced or metastatic hepatocellular carcinoma (HCC) previously treated with at least 1 systemic agent, with documented progressive disease, or documented adverse event(s) resulting in discontinuance of that (those) agents, stratified by level of GPC-3 expression (IHC score);Secondary Objective: 1. To compare treatment effect of GC33 vs. placebo on overall survival (OS) 2. To compare treatment effect of GC33 vs. placebo on disease control rate 3. To evaluate the tolerability and safety of GC33 when given as monotherapy in comparison to placebo using the NCI-CTCAE version 4.0 4. To further characterize the pharmacokinetic (PK) profile of GC33 5. To validate the GPC-3 immunohistochemistry(IHC) assay for analysis of GPC-3 expression ;Primary end point(s): Progression-free survival;Timepoint(s) of evaluation of this end point: When PFS data mature (about 24 months from FPFV) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival Time to progression Disease control rate ;Timepoint(s) of evaluation of this end point: Planned at the same time as primary endpoint | — |
Countries
Belgium, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Singapore, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed