Clinical trial NCT01204177: Assessing BAY86-9766 Plus Sorafenib for the Treatment of Liver Cancer.
Official title: A Phase II Trial of BAY86-9766 Plus Sorafenib as First Line Systemic Treatment for Hepatocellular Carcinoma (HCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Keywords: Hepatocellular carcinoma (HCC)
MEK inhibitor
Sorafenib
Disease control rate (DCR)
Safety
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2010-09-17
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: From first dose of combination treatment until last tumor evaluation
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 1st dose of study medication to last date of follow up
measure: Time To Progression (TTP)
timeFrame: 1st dose of study medication until disease progression
measure: Response Rate (RR)
timeFrame: 1st dose of study medication until last tumor evaluation
measure: Duration Of Response (DOR)
timeFrame: 1st dose of study medication until last tumor evaluation
measure: Safety: physical examination, vital signs, adverse events, safety lab
timeFrame: At day 1, 8, 15 of cycle 1 and 2 and day 1 of each next cycle until 30 days after EOT
measure: Patients reported hepatobiliary cancer symptoms and Health Related Quality of Life (HRQoL)
timeFrame: At day 1 of each cycle and within 7 day after the last treatment
measure: Pharmacokinetic (PK) profiles of BAY86-9766 and sorafenib to evaluate drug exposure (not in all patients)
timeFrame: Day -3, cycle 2 (day 1)
measure: Biomarkers
timeFrame: At screening, day 1 of cycle 1 - 4, EOT
Other outcomes:
Locations:
city: Shatin
country: Hong Kong
state: New Territories
city: Hong Kong
country: Hong Kong
city: Jung-gu
country: Korea, Republic of
state: Daegu Gwang''yeogsi
city: Goyang-si
country: Korea, Republic of
state: Gyeonggido
city: Busan
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Kaohsiung
country: Taiwan
city: Tainan
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Lim HY, Heo J, Choi HJ, Lin CY, Yoon JH, Hsu C, Rau KM, Poon RT, Yeo W, Park JW, Tay MH, Hsieh WS, Kappeler C, Rajagopalan P, Krissel H, Jeffers M, Yen CJ, Tak WY. A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma. Clin Cancer Res. 2014 Dec 1;20(23):5976-85. doi: 10.1158/1078-0432.CCR-13-3445. Epub 2014 Oct 7.