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The Phase III Study of Icaritin Versus HUACHANSU PIAN in Hepatocellular Carcinoma Subjects | Clinical Trials | Clareo Health

UNKNOWNPHASE3

The Phase III Study of Icaritin Versus HUACHANSU PIAN in Hepatocellular Carcinoma Subjects

Comparison of Efficacy and Safety of Icaritin Versus Cinobufotalin in First-line Treatment of Advanced Hepatocellular Carcinoma Subjects: a Multicenter, Randomized, Double-blind, Double-dummy Phase III Clinical Trial

NCT03236636•Beijing Shenogen Biomedical Co., Ltd

View on ClinicalTrials.gov

Summary

The enriched HBV-related advanced HCC patient population (composite biomarker score ≥ 2) and overall survival (OS) were compared between the two groups.

Detailed Description

The basis of enrichment design adjustment ： The latest published literature shows that the heterogeneity and immune tolerance of patients with hepatitis B virus (HBV) - related HCC are significantly correlated with a number of cytokines, including helper T cell subgroup 1 / 2 (Th1 / Th2) related factors. Moreover, the accumulated data show that the immunomodulatory effect of flavonoids including Icaritin is related to Th1 / Th2 factors. At the same time, the recent REACH2 study published in Lancet Oncology has successfully used serum alpha fetoprotein (AFP≥400) to enrich patients with advanced HCC. Based on the updated published data and our phase II clinical trial data, considering that the ongoing clinical trials are still in a blind state and no statistical analysis has been conducted, with consulting of clinical experts, regulatory agency advice, the protocol was amended and approved into adaptive enrichment design. Before unblended and SAP, the amendment protocol was prospectively pre-defined including sample size, patient population (CBS score positive), and event number for interim and final analysis. combined with the latest FDA clinical trial enrichment design guidelines (2019), several experts recommended to use the composite biomarkers, including IFN-γ , TNF - α and AFP, which may demonstrate the clinical advantages of the immunomodulation therapy with Icaritin for HBV-related advanced HCC patients in China with poor prognosis, but currently lack of treatment options. Definition of enriched HBV-related advanced HCC patient: Patient with serum composite biomarker score (CBS)≥2 Enrichment design amendment: Based on our previous phase II data of Icaritin collected from HBV-related advanced HCC patients and the related literature, we assume that the mOS of the enriched population (CBS≥2) is 420 days (14 months) in the experimental group and 240 days (8 months) in the HUACHASHU control group; the HR of the experimental group relative to the control group is 0.57. A total of 106 target death events and 130 evaluable subjects were required for the enrichment. Once the amendment protocol be effective, the enriched and non-enriched patients will be continuously randomized into the experimental and the control arms accordingly (1:1). When the number of enrolled cases reaches 280, or 60% of events (64) of 106 deaths has been observed in the enriched population, interim analysis will be performed.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Only patients who meet all the following criteria are included in the study:
•①Marrow: There is no blood transfusion and use of hematopoietic cell stimulating agent, including granulocyte colony stimulating factor (G-CSF)within 14 days before screening, platelet≥60×10E9/L, hemoglobin≥ 85g/L, white blood cell≥3.0×10E9/L; After a thorough measurement of the patient's condition, the above three items can be appropriately relaxed by the principal researchers at the research centre as: platelet 50 \~60×10E9/L, hemoglobin 80\~85g/L, white blood cell 2.5 \~3.0×10E9/L (contains critical values);
•②Liver: Total bilirubin≤1.5 times of the upper limit of normal(ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤5 × ULN; albumin≥ 28g/L;
•④ Kidney: Serum creatinine≤ 1.5 x ULN, or creatinine clearance rate≥ 50ml/min; 13) If HBV-DNA≥104 copies/ml(2000IU/ml), antiviral therapy must be done first, the patient can be included in the group until HBV-DNA\<104 copies /ml(2000IU/ml); and continue to take antiviral drugs, monitor liver function and hepatitis B virus load; 14) Women of childbearing age must receive pregnancy tests 14 days before treatment and the results are negative; Men of childbearing age need effective contraception during treatment and within 3 months after treatment; 15) Patients are volunteered to join the study, sign the informed consent, have good compliance and cooperate with follow-up; 16) The subjects do not participate in other clinical trials within 4 weeks before screening; If the subject fails in other test screening, but meets the requirements of this test, then can be enrolled.

Exclusion Criteria

•Patients who meet any of the following criteria are not allowed to enter the test:
•1. Imaging examination shows that HCC liver tumors are huge (≥60% of the liver volume), or cancer embolus of portal trunk (occupying ≥50% of the vascular diameter), or cancer embolus invading mesenteric vein or inferior vena cava;
•2. Middle or higher ascites which is clinically significant, it requires therapeutic abdominal paracentesis /drainage, or the Child-Pugh score \> 2;
•3. Local anticancer therapy (including surgery, ablation, hepatic arterial chemotherapy, embolization or radiotherapy) or major surgery was performed 28 days prior to randomization;
•4. Hepatocholangiocarcinoma and fibrolamellar cell carcinoma; In the past 5 years or at the same time, there were other malignancies, except cervical carcinoma in situ, previously treated basal cell carcinoma and superficial bladder tumor (Ta, Tis, T1);
•5. Pregnant or lactating women;
•6. The patient suffers from CTCAE classification type II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmia; and/or NYHA standard III to IV cardiac dysfunction.
•7. Allograft transplants including liver transplantation were performed previously, or a liver transplant was planned during the trial;
•8. Hepatic encephalopathy and / or hepatic nephropathy occurred within 6 months;
•9. Patient with active hepatitis C, that is, anti -HCV positive or HCV-RNA positive and abnormal liver function;
+9 more criteria

Locations (28)

Anhui Provincial Hospital

Hefei, Anhui, China

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Cancer Hospital Chinese Academy of Medical Sciences