Study to Investigate the Efficacy and Safety of CS1003 in Combination with Lenvatinib Compared to Placebo in Combination with Lenvatinib in Subjects with advanced liver cancer
- Conditions
- unresectable advanced hepatocellular carcinomaMedDRA version: 21.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003337-41-ES
- Lead Sponsor
- CStone Pharmaceuticals (Suzhou) Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 525
1. 18 years -75 years of age on the day of signing informed consent.
2. Fully informed of the study, with good compliance and willing to provide written informed consent. The informed consent must be signed before performing any protocol-related procedure that is not a part of subject’s routine medical care.
3. Subjects with pathohistologically or cytologically confirmed unresectable advanced HCC not eligible for locoregional therapy (Stage B or C based on Barcelona Clinic Liver Cancer [BCLC] staging system indicated in Appendix 14.6, not eligible for radical surgery and/or locoregional therapy, or subjects experienced progressive disease after surgery and/or locoregional therapy).
4. With at least one measurable lesion assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Appendix 14.2) within 14 days prior to the first dose of study treatment. Target lesions in the past radiation fields or that underwent local therapy (including interventional therapy or ablation), if confirmed as radiographic progression, are considered as measurable lesions.
5. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
6. Life expectancy = 3 months.
7. Child-Pugh = 6 (Child-Pugh A).
8. No prior systemic treatment for advanced HCC, including targeted therapy, chemotherapy, immunotherapy (immune checkpoint inhibitors, interferons, ILs), biological therapy (anti-cancer vaccines, cytokines, or growth factors), antibodies/drugs that target at any T cell co-regulatory protein (immune checkpoint), e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-OX-40, anti-CD137, anti-TIM-3, anti-LAG-3 antibodies, etc.
9. Subjects with hepatitis B virus (HBV) infection must have HBV DNA < 2000 IU/mL at the screening.
Subjects with positive HBsAg and/or positive HBV DNA who have accepted anti-HBV treatment prior to the first dose of study treatment for at least 2 weeks and are willing to continue receiving antiviral treatment while on study.
10. After the approval from local health authorities is obtained (if applicable), all subjects must provide unstained tumor tissue sections of adequate quality and the corresponding pathology report for biomarker analysis before randomization. During the screening, subjects only with imaging diagnosis must be confirmed by histology before enrollment. The tumor tissue sections are prepared using fresh or archived sample that has been archived for < 12 months.
11. Absolute neutrophil count (ANC) = 1.5 × 10^9 /L;
12. Platelet count = 75 × 10^9 /L;
13. Hemoglobin = 90 g/L
14. Serum albumin = 29 g/L
15. Serum creatinine = 1.5 × upper limit of normal range (ULN) or creatinine clearance (CL) = 60 mL/min (according to Cockcroft-Gault equation)
16. Serum total bilirubin = 2 × ULN.
17. Aspartate transaminase (AST) and alanine transaminase (ALT):
AST = 5 × ULN
ALT = 5 × ULN
18. Coagulation: International normalized ratio (INR) and prothrombin time (PT) = 1.5 × ULN.
19. Female subjects with childbearing potential must have negative serum pregnancy test result at screening. Female subjects with childbearing potential except those with documented sterilization operation or post-menopausal subjects, and male subjects and their partners must agree to use an effective contraceptive from the day of signing informed consent form (ICF), during the study and till at least 6 months after the last dose of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2
1. Fibrolamemellar carcinoma of liver, sarcomatoid carcinoma, cholangiocellular carcinoma or mixed hepatic cancer.
2. History of hepatic encephalopathy.
3. Gastrointestinal bleeding (e.g., hematemesis, melena) that is active or documented within the past 6 months.
4. Radiographic evidence of portal vein tumor thrombus (VP4), vena cava or heart involvement.
5. Malabsorption syndrome or inability to take oral medication due to other causes.
6. HBV and HCV co-infection. (Note: Subject who was HCV infected but is HCV RNA (-) at screening can be considered as not infected with HCV).
7. Palliative surgery, locoregional therapy (including interventional therapy, ablation, ethanol injection, etc.) or radiotherapy for liver lesions within 4 weeks prior to screening.
8. Uncontrolled pleural effusion, pericardial effusion that are symptomatic and requiring repeated drainage or oral diuretics at screening.
9. With ascites that is detectable in the physical examination at screening, or is symptomatic, or requires special care, e.g., repeated drainage or intraperitoneal drug infusion. (Note: Subjects with limited volume of ascites that is only identifiable by imaging can be enrolled.)
10. Hypertension uncontrolled by medication (i.e. systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg).
11. With another active malignancy in the past 5 years, except local curable cancers that have undergone curative therapy, e.g. basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer or prostate cancer, breast cancer in situ or cervical cancer in situ.
12. Subjects with central nerve system (CNS) metastasis.
13. Subjects with active autoimmune disease or history of autoimmune disease that probably will relapse or at risk of having these conditions (e.g., having received organ transplantation and require immune suppressant treatment). Subjects with type I diabetes mellitus, hypothyroidism that can be managed with thyroxine replacement, or dermatological condition that doesn't require systemic treatment (e.g., leukoderma, psoriasis or alopecia) are allowed to be enrolled. For any uncertainty, consultation with Sponsor’s medical monitor is recommended before the subject signs informed consent.
14. Subjects with major cardiovascular diseases (e.g., congestive heart failure, unstable angina, atrial fibrillation, severe arrhythmia, etc.); any of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months before enrollment; New York Heart Association (NYHA) grade = 2 congestive heart failure.
15. Presence of interstitial lung disease or non-infectious pneumonitis, whose symptoms might confound the evaluation or management of study treatment-associated pulmonary toxicity.
16. Any active infection (not including hepatitis virus infection) that requires intravenous infusion for systemic treatment within 2 weeks prior to the first dose of study treatment.
17. Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
18. Active pulmonary tuberculosis.
19. Any use of traditional Chinese medicine preparation with anti-HCC indication (e.g., elemene, Kanglaite, Cinobufacini, Xiaoaiping, Huai’er granule, Ganfule tablet, Jinlong capsule and Aidi) within 14 days prior to the first dose of study treatment.
20. Any use of systemic corticosteroid (> 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days prio
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method