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Advanced Hepatocellular CarcinomaPhase 2NCT01033240

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

A Phase 2 study testing CS-1008 2 mg/kg, Sorafenib and CS-1008 6/2 mg/kg in people with Advanced Hepatocellular Carcinoma and Liver Cancer, run by Daiichi Sankyo at 28 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CS-1008 2 mg/kg, Sorafenib and CS-1008 6/2 mg/kg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
172 participants
Where
28 sitesin 4 countries
Study dates
9 Jul 2010to 9 Sep 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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%)
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  • 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

Trial locations and contacts

28 sites in 4 countries.

28 sites in 4 countries

Japan9 sites

  • Chiba University Hospital

    Chiba, 260-8677

  • Hiroshima University

    Hiroshima, Hiroshima

  • Kanazawa University

    Kanazawa, Ishikawa-ken

  • Kurume University Hospital

    Kurume-shi, Fukuoka, 830-0011

  • Okayama University Hospital

    Okayama, 700-8558

  • Kinki University Hospital

    Osaka, Osaka-sayama, 589-8511

  • Osaka Med Center Cancer and Cardiovascular Disease

    Osaka, 537-8511

  • Musashino Red-Cross Hospital

    Tokyo, 180-8610

  • Yamaguchi University Hospital

    Ube, Yamaguchi

Other trials in Japan

Taiwan8 sites

  • Changhua Christian Hospital

    Changhua, 500

  • Chang Gung Memorial Hospital

    Chiayi City

  • Kaohiung Chang Gung Hospital

    Kaohsiung City, Niaosung Hsiang

  • Kaohslung Medical University Hospital

    Kaohsiung City, 807

  • National Cheng-Kung University Hospital

    Tainan, 704

  • Chi-Mei Medical Center

    Tainan, 73657

  • National Taiwan University Hospital

    Taipei

  • Chang Gung Medical Foundation-Linkuo

    Taoyuan, 33305

Other trials in Taiwan

South Korea7 sites

  • Keimyung University Dongsan Hospital

    Daegu, 700-712

  • Seoul National University Hospital

    Seoul, 110-744

  • Severance Hospital

    Seoul, 120-752

  • Samsung Medical Center

    Seoul, 135-710

  • Korea University Anam Hospital

    Seoul, 136-705

  • Catholic Univ. of Korea, Seoul St. Mary's Hospital

    Seoul, 137-701

  • Asan Medical Center

    Seoul, 138-736

Other trials in South Korea

United States4 sites

  • Kenmar Research Group

    Los Angeles, California, 90057

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • The Mount Sinai Medical Center

    New York, New York, 10029

  • Georgetown-Lombardi Cancer Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

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

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).

Being tested
CS-1008 2 mg/kg, Sorafenib, CS-1008 6/2 mg/kg, CS-1008 6/6 mg/kg, CS-1008 4 mg/kg
Keywords
Sorafenib, CS-1008, Advanced Liver Cancer
Medical subject headings
Liver Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CS-1008 2 mg/kgDrug

    On a once a week basis CS-1008 will be administered intravenously starting at 2 mg/kg.

  • SorafenibDrug

    Also called Nexavar

    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.

  • CS-1008 6/2 mg/kgDrug

    A 6 mg/kg loading dose of CS-1008 will be administered intravenously, followed by a 2 mg/kg/week maintenance dose on a once-a-week basis.

  • CS-1008 6/6 mg/kgDrug

    A 6 mg/kg loading dose of CS-1008 will be administered intravenously, followed by a 6 mg/kg/week maintenance dose on a once-a-week basis.

  • CS-1008 4 mg/kgDrug

    On a once a week basis CS-1008 will be administered intravenously at 4 mg/kg if tolerated.

  • CS-1008 6 mg/kgDrug

    On a once a week basis CS-1008 will be administered intravenously at 6 mg/kg if tolerated.

Study groups in NCT01033240
Study groupRoleWhat they receive
Safety Cohort 1 CS-1008 and SorafenibExperimentalCombination of CS-1008 and sorafenib; CS-1008 (2 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth twice daily) over 4 weeks observation, and may continue treatment until progression.
Receives: Drug: CS-1008 2 mg/kg; Drug: Sorafenib
Safety Cohort 2 CS-1008 and SorafenibExperimentalCombination of CS-1008 and sorafenib; CS-1008 (4 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth twice daily) over 4 weeks observation, and may continue treatment until progression.
Receives: Drug: Sorafenib; Drug: CS-1008 4 mg/kg
Safety Cohort 3 CS-1008 and SorafenibActive comparatorCombination of CS-1008 and sorafenib; CS-1008 (6 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth twice daily) over 4 weeks observation, and may continue treatment until progression.
Receives: Drug: Sorafenib; Drug: CS-1008 6 mg/kg
Treatment Group 1 CS-1008 and SorafenibExperimentalCombination 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 (N=50)
Receives: Drug: Sorafenib; Drug: CS-1008 6/2 mg/kg
Treatment Group 2 with CS-1008 and SorafenibExperimentalCombination 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 twice daily (N=50)
Receives: Drug: Sorafenib; Drug: CS-1008 6/6 mg/kg
Treatment Group 3 with Sorafenib AloneExperimentalSorafenib. Treatment Group 3: sorafenib twice daily (N=50)
Receives: Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to Progression (TTP) Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer

    Time to progression was defined as the time from randomization to the date of the first objective documentation of radiographic or symptomatic progression, whichever came first.

    Measured: Baseline up to approximately 2 years post-dose.

Secondary outcomes (3)

  1. Overall Survival Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer

    Overall survival (OS) was defined as the time from randomization to the date of death. The factors in the final model were treatment, Eastern Cooperative Oncology Group (ECOG) performance status, presence of extrahepatic metastasis and/or macrovessel invasion, and region.

    Measured: Baseline up to approximately 3 years 2 months post-dose.

  2. Best Overall Response and Objective Response Rate Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer

    The best overall response is the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], unconfirmed CR, unconfirmed PR, stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the participant withdraws from the study based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. If there is no tumor assessment after the first dose of study drug, the best overall response is classified as Inevaluable. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions. Objective response rate was defined as confirmed CR and confirmed PR.

    Measured: 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.

  3. Treatment-Emergent Adverse Events Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer

    Treatment-Emergent Adverse Events (TEAEs) were defined as those adverse events (AEs) that occurred, having been absent before the study, or worsened in severity after the initiation of study treatment administration. An AE that occurred more than 30 days after the last dose of study medication was not included as a TEAE unless it was considered related to treatment or the assessment of relatedness was missing.

    Measured: Baseline up to 30 days after last dose, up to approximately 3 years 2 months post-dose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2009 (estimated)
  2. Study start9 Jul 2010
  3. Primary completion13 Jul 2012
  4. Study completion9 Sep 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
172 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01033240
Sponsor's protocol ID
CS1008-A-U204
Status last verified
Apr 2021
First submitted
15 Dec 2009
Last updated
8 Apr 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 26071796

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CS-1008 2 mg/kg, Sorafenib and CS-1008 6/2 mg/kg in people with Advanced Hepatocellular Carcinoma and Liver Cancer, run by Daiichi Sankyo at 28 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Japan, Taiwan, South Korea, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to Progression (TTP) Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer (time frame: Baseline up to approximately 2 years post-dose.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01033240, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2021.

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