NCT03236636

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

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 312 (estimated)
• Sponsor: Beijing Shenogen Biomedical Co., Ltd · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Advanced HBV-Related Hepatocellular Carcinoma (HCC)

Interventions

Type	Name	Description
DRUG	Icaritin	Icaritin：600mg/time, 6 capsules/time(6×100mg/capsule), 2 times/day(30 minutes after breakfast, lunch and dinner), take orally, continuous administration until reach the standard of termination.
DRUG	HUACHANSU PIAN	HUACHANSU PIAN:Take orally 4 tablets/time(0.3g/tablet), 3 times/day(30 minutes after breakfast, lunch and dinner), continuous administration until reach the standard of termination.

Timeline

• Start date: 2017-09-08
• Primary completion: 2022-12-30
• Completion: 2022-12-30
• First posted: 2017-08-02
• Last updated: 2021-01-27

Locations

28 sites across 1 country: China