BASIL: Assessing BAY86-9766 Plus Sorafenib for the Treatment of Liver Cancer.

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT01204177

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

4.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular	Drug: BAY86-9766 MEK Inhibitor + Sorafenib	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial of BAY86-9766 Plus Sorafenib as First Line Systemic Treatment for Hepatocellular Carcinoma (HCC)

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Aug 1, 2011

Actual Study Completion Date :

Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1	Drug: BAY86-9766 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)

Arm

Intervention/Treatment

Experimental: Arm 1

Drug: BAY86-9766 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)

Outcome Measures

Primary Outcome Measures

Disease Control Rate (DCR) [From first dose of combination treatment until last tumor evaluation]

Secondary Outcome Measures

Overall Survival (OS) [1st dose of study medication to last date of follow up]
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]
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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Shatin	New Territories	Hong Kong
2	Hong Kong		Hong Kong
3	Jung-gu	Daegu Gwang''yeogsi	Korea, Republic of	700-721
4	Goyang-si	Gyeonggido	Korea, Republic of	410-769
5	Busan		Korea, Republic of	602-739
6	Seoul		Korea, Republic of	110-744
7	Seoul		Korea, Republic of	120-752
8	Seoul		Korea, Republic of	135-710
9	Seoul		Korea, Republic of	138-736
10	Singapore		Singapore	228510
11	Singapore		Singapore	258499
12	Kaohsiung		Taiwan	833
13	Tainan		Taiwan	736
14	Tainan		Taiwan
15	Taipei		Taiwan	100