CS1008- in Combination With Sorafenib Compared to Sorafenib Alone in Subjects With Advanced Liver Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT01033240
First received: December 15, 2009
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

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).


Condition Intervention Phase
Advanced Hepatocellular Carcinoma
Liver Cancer
Hepatic Cancer
Liver Neoplasms
Drug: CS-1008
Drug: sorafenib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • time to progression (TTP) for chemotherapy naive subjects with advanced hepatocellular carcinoma (HCC) [ Time Frame: time to progression, up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • overall survival (OS) [ Time Frame: time to progression, up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: March 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01033240

Locations
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
Korea University Anam Hospital
Seoul, Korea, Republic of, 136-705
Severance Hospital
Seoul, Korea, Republic of, 120-752
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
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
Sponsors and Collaborators
Daiichi Sankyo Inc.
  More Information

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT01033240     History of Changes
Other Study ID Numbers: CS1008-A-U204
Study First Received: December 15, 2009
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014