CS1008- in Combination With Sorafenib Compared to Sorafenib Alone in Subjects With Advanced Liver Cancer
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ClinicalTrials.gov Identifier: NCT01033240 |
Recruitment Status
:
Completed
First Posted
: December 16, 2009
Last Update Posted
: March 17, 2016
|
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Advanced Hepatocellular Carcinoma Liver Cancer Hepatic Cancer Liver Neoplasms | Drug: CS-1008 Drug: sorafenib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 172 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 Start Date : | March 2010 |
Actual Primary Completion Date : | November 2014 |
Actual Study Completion Date : | December 2014 |

Arm | Intervention/treatment |
---|---|
Experimental: Safety Cohort 1 CS-1008 and sorafenib
Combination of CS-1008 and sorafenib; CS-1008 (2 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth [PO] twice daily [BID]) over 4 weeks observation, and may continue treatment until progression.
|
Drug: CS-1008
On a once a week basis CS-1008 will be administered intravenously starting at 2 mg/kg, followed by 4 mg/kg if tolerated, followed by 6 mg/kg if tolerated.
Drug: sorafenib
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day. The total daily dose of sorafenib is 800 mg. The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Other Name: Nexavar
|
Experimental: Treatment Group 1 CS-1008 and sorafenib
Combination of CS-1008 and sorafenib. Treatment Group 1: CS-1008 (6 mg/kg [or as determined] loading, 2 mg/kg/week maintenance) + sorafenib twice daily {BID} (N=50)
|
Drug: CS-1008
On a once a week basis CS-1008 will be administered intravenously starting at 2 mg/kg, followed by 4 mg/kg if tolerated, followed by 6 mg/kg if tolerated.
Drug: sorafenib
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day. The total daily dose of sorafenib is 800 mg. The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Other Name: Nexavar
|
Active Comparator: Treatment Group 3 with sorafenib alone
Combination of CS-1008 and sorafenib. Treatment Group 3: sorafenib BID (N=50)
|
Drug: sorafenib
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day. The total daily dose of sorafenib is 800 mg. The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Other Name: Nexavar
|
Experimental: Safety Cohort 2 CS-1008 and sorafenib
Combination of CS-1008 and sorafenib; CS-1008 (4 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth [PO] twice daily [BID]) over 4 weeks observation, and may continue treatment until progression.
|
Drug: CS-1008
On a once a week basis CS-1008 will be administered intravenously starting at 2 mg/kg, followed by 4 mg/kg if tolerated, followed by 6 mg/kg if tolerated.
Drug: sorafenib
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day. The total daily dose of sorafenib is 800 mg. The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Other Name: Nexavar
|
Experimental: Safety Cohort 3 CS-1008 and sorafenib
Combination of CS-1008 and sorafenib; CS-1008 (6 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth [PO] twice daily [BID]) over 4 weeks observation, and may continue treatment until progression.
|
Drug: CS-1008
On a once a week basis CS-1008 will be administered intravenously starting at 2 mg/kg, followed by 4 mg/kg if tolerated, followed by 6 mg/kg if tolerated.
Drug: sorafenib
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day. The total daily dose of sorafenib is 800 mg. The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Other Name: Nexavar
|
Experimental: Treatment Group 2 with CS-1008 and sorafenib
Combination of CS-1008 and sorafenib. Treatment Group 2: CS-1008 (6 mg/kg [or as determined] loading, 6 mg/kg/week [or maximum tolerated dose {MTD}] maintenance) + sorafenib BID (N=50)
|
Drug: CS-1008
On a once a week basis CS-1008 will be administered intravenously starting at 2 mg/kg, followed by 4 mg/kg if tolerated, followed by 6 mg/kg if tolerated.
Drug: sorafenib
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day. The total daily dose of sorafenib is 800 mg. The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Other Name: Nexavar
|
- time to progression (TTP) for chemotherapy naive subjects with advanced hepatocellular carcinoma (HCC) [ Time Frame: time to progression, up to 2 years ]
- objective response rate (ORR) i.e. the proportion of subjects with the best response of complete response or partial response [ Time Frame: time to progression, up to 2 years ]
- overall survival (OS) [ Time Frame: time to progression, up to 2 years ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
-
Histologically or cytologically confirmed 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
- AFP level > 200 ng/mL
-
Advanced diseases
- Extrahepatic metastasis, OR
- Locally advanced diseases which are not amendable for surgical resection or other loco-regional therapies including transhepatic arterial (chemo)embolization (TACE or TAE) and local ablative therapy
- Measurable disease based on RECIST criteria (version 1.0) 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 109/L
- Platelet count ≥ 75 x 109/L
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance > 40 mL/min
- 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 subjects of childbearing potential must have a negative pregnancy test (serum or urine) result
- Subjects 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 IRB/IEC approved ICF before performance of any study specific procedures or tests
- Subjects 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, VEGF/VEGFR-inhibitors, epidermal growth factor receptor inhibitors or 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 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 IV congestive heart failure (Section 17.2)
- 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. Subjects 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 subject'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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01033240
United States, California | |
Kenmar Research Group | |
Los Angeles, California, United States, 90057 | |
United States, District of Columbia | |
Georgetown-Lombardi Cancer Center | |
Washington DC, District of Columbia, United States, 20007 | |
United States, New York | |
The Mount Sinai Medical Center | |
New York, New York, United States, 10029 | |
United States, Tennessee | |
Vanderbilt-Ingram Cancer Center | |
Nashville, Tennessee, United States, 37232 | |
Japan | |
Kurume University Hospital | |
Kurume-shi, Fukuoka, Japan, 830-0011 | |
Hiroshima University | |
Hiroshima-city, Hiroshima, Japan | |
Kanazawa University | |
Kanazawa, Ishikawa, Japan | |
Kinki University Hospital | |
Osaka, Osaka-sayama, Japan, 589-8511 | |
Osaka Med Center Cancer and Cardiovascular Disease | |
Higashinari-ku, Osaka, Japan, 537-8511 | |
Yamaguchi University Hospital | |
Ube, Yamaguchi, Japan | |
Chiba University Hospital | |
Chiba, Japan, 260-8677 | |
Okayama University Hospital | |
Okayama, Japan, 700-8558 | |
Musashino Red-Cross Hospital | |
Tokyo, Japan, 180-8610 | |
Korea, Republic of | |
Samsung Medical Center | |
Gangnam-gu, Seoul, Korea, Republic of, 135-710 | |
Keimyung University Dongsan Hospital | |
Daegu, Korea, Republic of, 700-712 | |
Seoul National University Hospital | |
Seoul, Korea, Republic of, 110-744 | |
Severance Hospital | |
Seoul, Korea, Republic of, 120-752 | |
Korea University Anam Hospital | |
Seoul, Korea, Republic of, 136-705 | |
Catholic Univ. of Korea, Seoul St. Mary's Hospital | |
Seoul, Korea, Republic of, 137-701 | |
Asan Medical Center | |
Seoul, Korea, Republic of, 138-736 | |
Taiwan | |
Chang Gung Memorial Hospital | |
Putz, Chiayi, Taiwan | |
Kaohiung Chang Gung Hospital | |
Kaohsiung, Niaosung Hsiang, Taiwan | |
Chi-Mei Medical Center | |
Liouying, Tainan County, Taiwan, 736 | |
Changhua Christian Hospital | |
Changhua, Taiwan, 500 | |
Kaohslung Medical University Hospital | |
Kaohsiung, Taiwan, 807 | |
National Cheng-Kung University Hospital | |
Tainan city, Taiwan, 704 | |
National Taiwan University Hospital | |
Taipei, Taiwan | |
Chang Gung Medical Foundation-Linkuo | |
Taoyuan, Taiwan, 33305 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Daiichi Sankyo, Inc. |
ClinicalTrials.gov Identifier: | NCT01033240 History of Changes |
Other Study ID Numbers: |
CS1008-A-U204 |
First Posted: | December 16, 2009 Key Record Dates |
Last Update Posted: | March 17, 2016 |
Last Verified: | February 2016 |
Additional relevant MeSH terms:
Carcinoma Carcinoma, Hepatocellular Liver Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Liver Diseases |
Sorafenib Niacinamide Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Vitamin B Complex Vitamins Micronutrients Growth Substances Physiological Effects of Drugs |