Clinical trial NCT01033240: CS1008- in Combination With Sorafenib Compared to Sorafenib Alone in Subjects With Advanced Liver Cancer
Official title: Clinical Study Protocol Phase 2, Randomized Study of CS-1008 in Combination With Sorafenib Compared to Sorafenib Alone as First-Line Systemic Therapy in Subjects With Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Hepatocellular Carcinoma
Liver Cancer
Hepatic Cancer
Liver Neoplasms
Keywords: Sorafenib
CS-1008
Advanced Liver Cancer
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2009-12-16
Enrollment: 172
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 this study is to determine the safety and efficacy of CS-1008 in combination with sorafenib to sorafenib alone for treating liver cancer. Approximately 160 participants will take part in this study at approximately 22 sites (4 in the US, 8 in Japan, and 10 in Asia).


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed hepatocellular carcinoma (HCC) or clinical diagnosis of HCC when the following criteria are all met:

  * History of chronic hepatitis and/or cirrhosis of liver;
  * Typical features of HCC demonstrated in dynamic imaging studies, such as three-phase computed tomography (CT); AND
  * Alpha-fetoprotein (AFP) level \> 200 ng/mL
* Advanced diseases

  * Extrahepatic metastasis, OR
  * Locally advanced diseases which are not amenable for surgical resection or other loco-regional therapies including transhepatic arterial (chemo) embolization (TACE or TAE) and local ablative therapy
* Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 of at least 1 untreated target lesion that can be measured in 1 dimension
* At least 18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Child-Pugh class A
* Life expectancy of at least 12 weeks
* Adequate organ and bone marrow function as assessed by clinical laboratory evaluations:

  * Hemoglobin ≥ 8.5 g/dL (transfusion and/or growth factor support allowed)
  * Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L
  * Platelet count ≥ 75 x 10\^9/L
  * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance \> 40 mL/min
  * Aspartate Aminotransferase (AST) and alkaline phosphatase ≤ 5.0 x ULN
  * Total bilirubin ≤ 1.5 x ULN
* Serum amylase and lipase ≤ 1.5 x ULN
* Women of childbearing potential must be willing to consent to using effective contraception (eg, abstinence, hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device) while on treatment and for 3 months thereafter. Men who are the partner of a woman of childbearing potential must be willing to consent to using effective contraception (eg, vasectomy or barrier with spermicide) while on treatment and for 3 months thereafter
* All female participants of childbearing potential must have a negative pregnancy test (serum or urine) result
* Participants must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an International Review Board (IRB)/ Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) before the performance of any study specific procedures or tests
* Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria:

* Any prior systemic therapy for HCC, including systemic chemotherapy (prior exposure to chemotherapy by TACE is allowed), immunotherapy, sorafenib or other Raf kinase inhibitors, Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor (VEGFR)-inhibitors, epidermal growth factor receptor inhibitors or mechanistic target of rapamycin (mTOR) inhibitors
* Radiotherapy or major surgical procedure within 4 weeks of the screening/baseline visit or minor surgical procedures (eg, core biopsy or fine needle aspiration) within 2 weeks of the screening/baseline visit
* Anticipation of need for radiotherapy (RT) or a major surgical procedure during the study
* Any investigational agent within 4 weeks before the screening/baseline visit
* History of any of the following conditions within 6 months before the screening/baseline visit:

  * Myocardial infarction with significant impairment of cardiac function (eg, ejection fraction ≤ 30%)
  * Severe/unstable angina pectoris
  * New York Heart Association (NYHA) class III or intravenous (IV) congestive heart failure
  * Clinically significant pulmonary disease (eg, severe chronic obstructive pulmonary disease or asthma)
* Clinically active brain metastases (defined as untreated, symptomatic or requiring steroids or anticonvulsants medications to control associated symptoms), uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis. Participants with treated brain metastasis will be included in the study if they have recovered from the acute, toxic effects of radiotherapy. A minimum of 15 days must have elapsed between the end of RT and the screening/baseline visit
* History of organ transplantation
* Clinically significant, severe, active infection requiring IV antibiotics
* Known history of human immunodeficiency virus (HIV) infection
* History of prior sensitivity reaction to any components of CS-1008 or sorafenib formulations
* History of a second malignancy, with the exception of in situ cervical cancer or adequately treated basal cell or squamous cell carcinoma of the skin
* Pregnant or breast feeding
* Serious intercurrent medical illnesses that, in the opinion of the Investigator, would impair the participant's ability to provide informed consent or unacceptably reduce the safety of the proposed treatment
* Clinically significant (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] grade ≥ 3) gastrointestinal bleeding in the past 12 months or current active gastrointestinal bleeding
* Presence of esophageal varices at risk of bleeding, such as large esophageal/gastric varices or those with red sign, or active peptic ulcer with or without exposed vessels at risk of bleeding (as documented by endoscopy)
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 6 months

Primary outcomes:
measure: Time to Progression (TTP) Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
timeFrame: Baseline up to approximately 2 years post-dose.
Secondary outcomes:
measure: Overall Survival Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
timeFrame: Baseline up to approximately 3 years 2 months post-dose.
measure: Best Overall Response and Objective Response Rate Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
timeFrame: Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 3 years 2 months post-dose.
measure: Treatment-Emergent Adverse Events Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
timeFrame: Baseline up to 30 days after last dose, up to approximately 3 years 2 months post-dose.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Kenmar Research Group
state: California
city: Washington
country: United States
facility: Georgetown-Lombardi Cancer Center
state: District of Columbia
city: New York
country: United States
facility: The Mount Sinai Medical Center
state: New York
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Hiroshima-city
country: Japan
facility: Hiroshima University
state: Hiroshima
city: Kanazawa
country: Japan
facility: Kanazawa University
state: Ishikawa
city: Osaka
country: Japan
facility: Kinki University Hospital
state: Osaka-sayama
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka Med Center Cancer and Cardiovascular Disease
city: Tokyo
country: Japan
facility: Musashino Red-Cross Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Catholic Univ. of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Kaohsiung
country: Taiwan
facility: Kaohiung Chang Gung Hospital
state: Niaosung Hsiang
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Chiayi City
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohslung Medical University Hospital
city: Tainan city
country: Taiwan
facility: National Cheng-Kung University Hospital
city: Tainan
country: Taiwan
facility: Chi-Mei Medical Center
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Linkuo
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
citation: Cheng AL, Kang YK, He AR, Lim HY, Ryoo BY, Hung CH, Sheen IS, Izumi N, Austin T, Wang Q, Greenberg J, Shiratori S, Beckman RA, Kudo M; Investigators' Study Group. Safety and efficacy of tigatuzumab plus sorafenib as first-line therapy in subjects with advanced hepatocellular carcinoma: A phase 2 randomized study. J Hepatol. 2015 Oct;63(4):896-904. doi: 10.1016/j.jhep.2015.06.001. Epub 2015 Jun 10.