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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

Phase 2
18 Years
Open (Enrolling)
Advanced Hepatocellular Carcinoma, Liver Cancer, Hepatic Cancer, Liver Neoplasms

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Trial Information

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

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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

time to progression (TTP) for chemotherapy naive subjects with advanced hepatocellular carcinoma (HCC)

Outcome Time Frame:

time to progression, up to 2 years

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

March 2010

Completion Date:

September 2012

Related Keywords:

  • Advanced Hepatocellular Carcinoma
  • Liver Cancer
  • Hepatic Cancer
  • Liver Neoplasms
  • Neoplasms
  • Carcinoma
  • Liver Neoplasms
  • Carcinoma, Hepatocellular



Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
The Mount Sinai Medical CenterNew York, New York  10029
Kenmar Research GroupLos Angeles, California  90057
Georgetown-Lombardi Cancer CenterWashington DC, District of Columbia  20007