Carcinoma, Hepatocellular
Conditions
Keywords
Hepatocellular carcinoma (HCC), MEK inhibitor, Sorafenib, Disease control rate (DCR), Safety
Brief summary
This study investigates the safety and efficacy of the combination therapy with BAY86-9766 and sorafenib in patients with liver cancer. Safety will be determined by laboratory and other evaluations. Efficacy of the combination BAY86-9766 and sorafenib will be determined by disease control rate, overall survival, time to progression, response rate and duration of response.
Interventions
DRUGBAY86-9766 MEK Inhibitor + Sorafenib
All patients who meet the entry criteria will receive BAY86-9766 50mg (2x20mg + 1x10mg capsules) twice daily in combination with sorafenib 800 mg (2x200 mg tablets bid). During the first 3 weeks they will receive a reduced dose of sorafenib: 600 mg / daily (1x200mg tablet in the morning + 2x200mg tablets in the evening) daily. This dose will be increased to the standard dose of 800 mg (400 mg bid) if no major side effects occur. Treatment until PD or until one of the withdrawal criteria for this study is met as described in the protocol (e.g. radiological progression or clinical progression)
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or Female age \>/= 18 years of age * Life expectancy \>/= 12 weeks * Histologically or cytologically confirmed diagnosis of HCC, unresectable advanced or metastatic * Liver function status of Child-Pugh class A. Child-Pugh status based on clinical findings and laboratory results during the screening period * Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 * Patients must have at least one naïve (not previously treated by locoregional therapy) uni-dimensional measurable lesion by CT or MRI according to RECIST 1.1 * Adequate bone marrow, liver and renal function
Exclusion criteria
* Previous or concurrent cancer other than HCC, except for cervical carcinoma in situ, basal cell carcinoma, superficial bladder tumors. * History of cardiac disease: Congestive heart failure (CHF), unstable angina, arrhythmias, Uncontrolled hypertension * Clinically significant GI bleeding (CTCAE grade 3 or higher) within 30 days * Renal failure requiring hemo- or peritoneal dialysis * Known human immunodeficiency virus (HIV) infection * Known history or symptomatic metastatic brain or meningeal tumors * History of organ allograft. * History of interstitial lung disease (ILD). * Excluded previous therapies and medications: * Prior use of systemic anti-cancer treatment for HCC including cytotoxic chemotherapy, targeted agents, or any experimental therapy * Radiotherapy within 4 weeks prior to start of study treatment * Any other investigational agents within 4 weeks from the first dose of study treatment * Major surgery within 4 weeks of start of study * Concomitant use of strong inhibitors and strong inducers of CYP3A4
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease Control Rate (DCR) | From first dose of combination treatment until last tumor evaluation |
Secondary
| Measure | Time frame |
|---|---|
| Time To Progression (TTP) | 1st dose of study medication until disease progression |
| Response Rate (RR) | 1st dose of study medication until last tumor evaluation |
| Duration Of Response (DOR) | 1st dose of study medication until last tumor evaluation |
| Overall Survival (OS) | 1st dose of study medication to last date of follow up |
| Patients reported hepatobiliary cancer symptoms and Health Related Quality of Life (HRQoL) | At day 1 of each cycle and within 7 day after the last treatment |
| Pharmacokinetic (PK) profiles of BAY86-9766 and sorafenib to evaluate drug exposure (not in all patients) | Day -3, cycle 2 (day 1) |
| Biomarkers | At screening, day 1 of cycle 1 - 4, EOT |
| Safety: physical examination, vital signs, adverse events, safety lab | At day 1, 8, 15 of cycle 1 and 2 and day 1 of each next cycle until 30 days after EOT |
Countries
Hong Kong, Singapore, South Korea, Taiwan
Outcome results
None listed