Clinical trial NCT00492752: A Randomized, Double-Blinded, Placebo-Controlled Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Official title: A Randomized, Double-blinded, Placebo-controlled Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2007-06-27
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is

* Find out if patients receiving Sorafenib will live longer
* Find out if Sorafenib has any effect on patient reported outcomes
* Find out if Sorafenib prevents the growth or shrinks liver tumors and / or their metastases
* Determine the pharmacokinetics (PK) in patients with liver cancer


Eligibility criteria: Inclusion Criteria:

* Ages eligible for study: 18 years and above, Genders eligible for study: both
* Patients who have a life expectancy of at least 12 weeks
* Patients with advanced Hepatocellular carcinoma (HCC) (unresectable, and/or metastatic) which has been histologically or cytologically documented
* Patients must have at least one tumor lesion that meets both of the following criteria

  1. Accurately measured in at least one dimension according to Response Evaluation Criteria in Solid Tumors (RECIST)
  2. Not been previously treated with local therapy
* Patients who have received local therapy, such as surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible. Previously treated lesions will not be selected as target lesions. Local therapy must be completed at least 4 weeks prior to the baseline scan
* Patients who have an Eastern Co-operative Oncology Group (ECOG) Performance Status of 0, 1, or 2

Exclusion Criteria:

* Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta \[Noninvasive papillary carcinoma\], Tis \[Carcinoma in situ: "flat tumor"\]\&T1 \[Tumor invades subepithelial connective tissue\]). Any cancer curatively treated \> 3 years prior to entry is permitted
* History of cardiac disease
* Active clinically serious infections
* Known history of human immunodeficiency virus (HIV) infection
* Known central nervous system (CNS) tumors including metastatic brain disease
* Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
Secondary outcomes:
measure: Time to Symptomatic Progression (TTSP)
timeFrame: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
measure: Time to Progression (TTP)
timeFrame: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
measure: Disease Control
timeFrame: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
measure: Change in Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) Score From Baseline to Cycle 1 and Cycle 3
timeFrame: Baseline up to Cycle 1 and Cycle 3. From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
measure: Change in Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Score From Baseline to Cycle 3 and End of Treatment
timeFrame: Baseline up to Cycle 3 and end of treatment. From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
measure: Number of Participants With Different Tumor Response
timeFrame: From randomization/start of treatment of the first subject until approximately 23 months after randomization when the subjects on placebo were offered the option to crossover to sorafenib treatment
measure: Duration of Response
timeFrame: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
measure: Time to Response
timeFrame: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
measure: Area Under the Curve From Time 0 to 12 Hours Post-dose (AUC 0-12) After 21 Days of Sorafenib Treatment
timeFrame: PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1
measure: Normalized Area Under the Curve (AUC Norm) After 21 Days of Sorafenib Treatment
timeFrame: PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1
measure: Maximum Concentration (Cmax) After 21 Days of Sorafenib Treatment
timeFrame: PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1
measure: Normalized Maximum Concentration (Cmaxnorm) After 21 Days of Sorafenib Treatment
timeFrame: PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1
measure: Time of Maximum Concentration (Tmax) After 21 Days of Sorafenib Treatment
timeFrame: PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1
Other outcomes:
Locations:
city: Hefei
country: China
state: Anhui
city: Guangzhou
country: China
state: Guangdong
city: Guangzhou
country: China
state: Guangdong
city: Wuhan
country: China
state: Hubei
city: Nanjing
country: China
state: Jiangsu
city: Nanjing
country: China
state: Jiangsu
city: Dalian
country: China
state: Liaoning
city: Dalian
country: China
state: Liaoning
city: Hangzhou
country: China
state: Zhejiang
city: Beijing
country: China
city: Beijing
country: China
city: Chongqing
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Tianjin
country: China
city: Seoul
country: Korea, Republic of
state: Seoul Teugbyeolsi
city: Daegu
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Changhua
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16.
citation: Cheng AL, Guan Z, Chen Z, Tsao CJ, Qin S, Kim JS, Yang TS, Tak WY, Pan H, Yu S, Xu J, Fang F, Zou J, Lentini G, Voliotis D, Kang YK. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: subset analyses of the phase III Sorafenib Asia-Pacific trial. Eur J Cancer. 2012 Jul;48(10):1452-65. doi: 10.1016/j.ejca.2011.12.006. Epub 2012 Jan 10.
citation: Bruix J, Cheng AL, Meinhardt G, Nakajima K, De Sanctis Y, Llovet J. Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies. J Hepatol. 2017 Nov;67(5):999-1008. doi: 10.1016/j.jhep.2017.06.026. Epub 2017 Jul 4.