Neoplasms

All Conditions

Digestive System Diseases

Infections

Skin and Connective Tissue Diseases

Carcinoma

Carcinoma, Hepatocellular

Yaws

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

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.

HUANCHANSU 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.

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.

Icaritin

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.

HUACHANSU PIAN

Yan Sun, MD

Shukui Qin

Yueyin Pan

Kangsheng Gu

Chengxu Cui, MD

Yunbo Zhao

Wei Hou

Chunyi Hao

Lingzhan Meng

Bin Hu

Qian Chen

Bangde Xiang

Juan Meng

Ruixing Zhang

Wang Ma

Peiguo Cao

Shukui Qin, MD

Yongqian Su

Aibing Xu

Wei Li

Wei Wu

Hongbo Ji

Yuping Sun

Jianhua Shi

Zhiqiang Meng

Ying Zhang

Yi Li

Gongying Chen

Yabing Guo

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

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.

multicenter, randomized, double-blind, double-dummy, adaptive enrichment design

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

Baseline expression or expression changes of programmed cell death ligand 1 (PD-L1), heterogeneous ribonucleoprotein A2/B1 (hnRNPAB1) and interleukin -6 (IL-6) and so on.

Genetic variation(Liver cancer driver genes and hotspot gene mutations, such as IDH1/2, JAK2/3, PD-L1/2), expression levels of oncogenes and immune related genes(Gene copy number and RNA expression level) and epigenetics cohort analysis

OS is defined as the time from randomization to died from any cause. For the subjects who failed to visit, deletion is performed on the final date of knowing the survival of the subjects, for subjects who still survive, deletion is performed on the data expiration date.

PFS is defined as the date from randomization to the first radiographic record of disease progression or death (whichever occurs first). See the Statistical Analysis Plan (SAP) for the definition of PFS deletion rule.

TTP is defined as the date from randomization to the first radiographic record of disease progression, see the Statistical Analysis Plan(SAP) for the definition of TTP deletion rule.

ORR is defined as the proportion of subjects achieving optimal overall efficacy such as CR or partial remission (PR).

DCR is defined as the proportion of subjects achieving optimal overall efficacy such as CR, PR or stable disease (SD).

Quality of life (QOL) changes: Quality of life scores are assessed with EORTC QLQ-C30 and compared with baseline values.

Quality of life (QOL) changes: Quality of life scores are assessed with EORTCQLQ-HCC-18 and compared with baseline values.

Chinese Academy of Medical Sciences

NanJing PLA 81 Hospital

Peking University Cancer Hospital & Institute

Beijing Hospital

Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Jinan Central Hospital

Linyi Tumour Hospital

The First Affiliated Hospital of Anhui Medical University

Anhui Provincial Hospital

The First Affiliated Hospital with Nanjing Medical University

The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China

Nanfang Hospital, Southern Medical University

First People's Hospital of Foshan

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Hebei Medical University Fourth Hospital

The First Hospital of Jilin University

Haikou People's Hospital

Fudan University

West China Hospital

Chongqing Traditional Chinese Medicine Hospital

Chifeng Municipal Hospital

The Affiliated Hospital of Hangzhou Normal University

The First Affiliated Hospital of Zhengzhou University

Guilin Medical University, China

The Third Xiangya Hospital of Central South University

Yunnan Provincial Hospital of Traditional Chinese Medicine

The Sixth People's Hospital of Shenyang

Beijing Shenogen Biomedical Co., Ltd

Antineoplastic Agents

All Drugs and Chemicals

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

400mg/time, 2 tablets/time(2×200mg/tablet), 2times/day(Fasting), take orally, continuous administration until reach the standard of termination.

Sorafenib Tosylate Tablets

The primary efficacy index of this study is to compare the OS of the two groups.

Icaritin is a newly discovered small molecular compound which is high selective ERa36 modulators ,the preclinical PK\&PD and toxicity studies showed it can inhibit the growth of HCC cancer cells both in vitro and in vivo, combining clinical data perhaps it will be a very promising new drug to treat hepatocellular carcinoma (HCC) by targeting this nongenomic pathway. Shenogen decided to further investigate the efficacy and safety of Icaritin and to explore potential gene targets for treating HCC.

The results of phase I study showed Icaritin has good safety and tolerance. The biological availability of Icaritin after meal is high and the half-life is relatively short.

The phase Ib study enrolled 28 subjects. Among the 18 HCC subjects, 12 subjects received treatment in the oral administration group with 600 mg once, twice per day, after meal 30 minutes, 6 subjects received treatment in the oral administration group with 800 mg once, twice per day, after meal 30 minutes. The results showed that in the 600mg group there are 12 HCC patients whose therapeutic efficacy is evaluable now, one case of PR (10%), 5 cases of SD (50%) and 4 cases of PD (40%) were observed.Safety data showed that totally 24 AEs are probably related to investigational drug. Among them, 19 AEs are grade I, 5 AEs are grade II, no grade III or above AE.

The Phase III Study of Icaritin Versus Sorafenib in PD-L1 Positive Advanced Hepatocellular Carcinoma Subjects

Comparison of Efficacy and Safety of Icaritin Versus Sorafenib in First-line Treatment of PD-L1 Positive Advanced Hepatocellular Carcinoma Subjects: a Multicenter, Randomized, Opened Phase III Clinical Trial

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Eastern Theater General Hospital,QinHuai District Medical Area

Chinese PLA General Hospital

General Hospital of Chinese Armed Police Forces

Linyi Cancer Hospital

Tianjin Medical University Cancer Institute and Hospital

The Fourth Hospital of Hebei Medical University

Hunan Cancer Hospital

307 Hospital of PLA

Henan Cancer Hospital

Jilin Provincial Tumor Hospital

First Affiliated Hospital of Harbin Medical University

First Affiliated Hospital Bengbu Medical College

The First Affiliated Hospital of Soochow University

Tongji Hospital

Beijing YouAn Hospital

Breast Neoplasms

Breast Diseases

Skin Diseases

Estrogens

50mg,100mg,200mg,300mg,400mg,500mg ascending-multiple oral dose, Qd, single dose and continuing dose 28 days, to assess the safety,tolerance and pharmacokinetics of icaritin

Ying Fan, MD

Binghe Xu, MD

To assess safety, tolerance and PK profile of different doses(50mg,100mg,200mg,300mg, 400mg, 500mg,QD)of Icaritin in advanced breast cancer Patients in China

ERa36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated "nongenomic" signaling pathway. Membrane-initiated estrogen signaling has been linked to rapid responses to estrogen and generally activates signaling pathways like MAPK/ERK, phosphatidylinositol-3-kinase, and protein kinase C pathways. Preclinical study demonstrated that ERa36 was expressed in tumor cells and might be the driving force of breast cancer cell proliferation. 40% of breast cancer tumors which used to be considered as ER negative also express ERa36. In the former study the investigators found that 40% of ERa66-positive breast cancer patients express high levels of ERa36 in their tumors, and this subset of patients are less likely to benefit from tamoxifen treatment compared with those with ERa66-positive/ERa36-negative tumors.

Icaritin is a newly discovered small molecular compound which is high selective ERa36 modulators and perhaps will be a very promising new drug to treat advanced breast cancer by targeting this nongenomic pathway. It was showed that it can inhibit the growth of breast cancer cells both in vitro and in vivo. The investigators have completed the preclinical PK\&PD and toxicity studies in animals and now move on to test it in a FIM clinical trial.

Phase I Study of Novel Estrogen Receptor(ER) a36 Modifier Icaritin in Advanced Breast Cancer Patients

A Phase I ,Single Center, Open-labeling, Single and Dose-escalating Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of Oral Novel ERa36 Modifier Icaritin in Advanced Breast Patients

to find the dose-limiting toxicity(DLT)and maximal tolerated dose(MTD)of icaritin in breast cancer patients

xubinghe

600mg,800mg two doses, Bid, continuous dosing for 56 days, to assess the safety,tolerance,pharmacokinetics and efficacy of icaritin

Bing he Xu, MD

to assess the safety, tolerability，PK and efficacy profile of two doses (600mg,800mg,BID) of Icaritin in advanced solid tumor patients in China

Estrogen receptor,ERa36, predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated "nongenomic" signaling pathway. Membrane-initiated estrogen signaling has been linked to rapid responses to estrogen and generally activates signaling pathways like the mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERK), phosphatidylinositol-3-kinase, and protein kinase C pathways. Preclinical study demonstrated that ERa36 was expressed in tumor cells and might be the driving force of breast cancer cell proliferation. 40% of breast cancer tumors which used to be considered as ER negative also express ERa36. In the former study the investigators found that 40% of ERa66-positive breast cancer patients express high levels of ERa36 in their tumors, and this subset of patients are less likely to benefit from tamoxifen treatment compared with those with ERa66-positive/ERa36-negative tumors.

Icaritin is a newly discovered small molecule with selective ERa36 modulating capability and the potential as a very promising new drug to treat advanced breast cancer and hepatocellular carcinoma (HCC) by targeting this nongenomic pathway. Studies showed that it can inhibit the growth of cancer cells both in vitro and in vivo. The investigators have completed the preclinical pharmacokinetic, pharmacodynamic (PK\&PD) and toxicity studies in animals and now move on to test it in a phase Ib clinical trial.

A Phase Ib Study to Assess Safety and Efficacy of Oral Icaritin in Advanced Solid Tumors

A Phase Ib ,Single Center, Open-labeling, Multiple Oral Dose Study to Assess the Safety, Tolerability，PK and Efficacy Profile for Advanced Solid Tumor Patients in China

Internal medicine director,Cancer institute & hospital

Icaritin 600 mg orally, twice daily for a total daily dose of 1200 mg

ShuKui Qin, MD

The primary objective of the study is to assess the time to progression (TTP) in patients with advanced HCC treated with Icaritin .

The Phase II Study of Icaritin in Patients With Advanced Hepatocellular Carcinoma

An Open-label,Single-arm Phase II Study of Icaritin in Patients With Advanced Hepatocellular Carcinoma

The study will be an open-label, single-armed study to evaluate the clinical benefit of Icaritin 600 mg twice daily with oral administration for total of 1200 mg daily added to Best Supportive Care in patients with advanced HCC.

PFS is defined as the time from the date of the first dose of study drug to first documentation of objective disease progression or to death on study due to any cause, whichever occurs first. It will be analyzed in the same way as TTP.

OS: This is defined as the time from the date of first study dose to the date of death, regardless of the cause of death. Patients who were alive at the time of the analysis will be censored at the date of the last follow up assessment. Patients without follow up assessment will be censored at the day of last dose and patients with no post baseline information will be censored at the time of first study dose. Overall survival is defined as the length of time from first dose of treatment until death. It will be analyzed in the same way as TTP.

ORR: it is defined as the percentage of the patients achieving remission (including PR and CR) of tumors during treatment or within 30 days after the initiative treatment as confirmed by the RECIST1.1.

DCR: during first-line therapy is defined as SD for 8 weeks or longer, CR plus PR as determined by the RESIST 1.1 criteria for patients with measurable disease.

Objective response rate and disease control rate will be determined along with 95% confidence intervals.

The descriptive analysis will be used for the data from quality of life questionnaire (EORTC QLQ-C30 V3.0 and HCC-18).

To assess the safety and tolerability of Icaritin in patients with advanced hepatocellular carcinoma

Qingdao University

600 mg (6 x 100 mg capsules) icaritin administered orally twice daily (30 minutes after breakfast and dinner, respectively) until treatment discontinuation criteria are met.

1200 mg (4 x 300 mg tablets) huachansu administered orally three times a day (30 minutes after breakfast, lunch and dinner, respectively) until treatment discontinuation criteria are met.

Huachansu

Jihui Hao, MD

JianBin Wu, Doctor

Hongbo Ji, Doctor

A study to evaluate the efficacy and safety of icaritin versus huachansu in the first-line treatment of unresectable hepatocellular carcinoma with poor conditions and biomarker enrichment.

This is a prospective, randomized, parallel-controlled, double-blind, double-dummy, multicenter, phase III clinical trial. Patients with poor conditions and biomarker enrichment will be randomly assigned in a 2:1 ratio to receive either icaritin or huachansu as the first-line treatment until unacceptable toxic effects and loss of clinical benefit. A total of 261 participants with 206 deaths are required. The primary endpoint is overall survival (OS) in the full analysis set (FAS) population.

Icaritin Soft Capsule Versus Huachansu Tablet in the First-line Treatment of Unresectable Hepatocellular Carcinoma With Poor Conditions and Biomarker Enrichment (Biomarker Enrichment Study of Poor Prognosis HCC Patients, BESTPOP)

A Prospective, Randomized, Parallel-Controlled, Double-Blind, Double-Dummy, Multicenter, Phase III Clinical Trial of Icaritin Soft Capsule Versus Huachansu Tablet in the First-line Treatment of Unresectable Hepatocellular Carcinoma With Poor Conditions and Biomarker Enrichment (Biomarker Enrichment Study of Poor Prognosis HCC Patients, BESTPOP)

Defined as the time from randomization to death from any cause

Defined as the percentage of participants who are alive at 9, 12, 18 months following randomization

Defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator and IRC according to RECIST v1.1

Defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator and IRC according to RECIST v1.1

Defined as the percentage of participants with complete response (CR) or partial response (PR), as determined by the investigator and IRC according to RECIST v1.1

Defined as the percentage of participants with complete response (CR), partial response (PR) or stable disease (SD), as determined by the investigator and IRC according to RECIST v1.1

Defined as the time from randomization to first deterioration, i.e., decrease or increase from baseline of ≥ 10 points in the following EORTC QLQ-C30 and EORTC QLQ-HCC18 subscales respectively, maintained for two consecutive assessments or one assessment followed by death from any cause within 4 weeks:

Defined as all untoward medical events in a participant administered the study drug, which can be symptoms, signs, diseases or laboratory abnormalities, irrespective of the causality with the study drug.

The type, incidence, severity, and relationship with study drugs of adverse events (AEs) will be evaluated.

Defined as trough plasma concentration（Cmin）of icaritin and its metabolites

Defined as maximum plasma concentration (Cmax) of icaritin and its metabolites

Defined as Mean area under the concentration-time curve during the dosing interval (AUC0-t) of icaritin and its metabolites at steady state

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Phase III Study of Icaritin Versus HUACHANSU PIAN in Hepatocellular Carcinoma Subjects	NCT03236636	Advanced HBV-Re...	Icaritin HUACHANSU PIAN	18 Years -	Beijing Shenogen Biomedical Co., Ltd
The Phase III Study of Icaritin Versus HUACHANSU PIAN in Hepatocellular Carcinoma Subjects	NCT03236636	Advanced HBV-Re...	Icaritin HUACHANSU PIAN	18 Years -	Beijing Shenogen Biomedical Co., Ltd
The Phase III Study of Icaritin Versus Sorafenib in PD-L1 Positive Advanced Hepatocellular Carcinoma Subjects	NCT03236649	Hepatocellular ...	Icaritin Sorafenib Tosyl...	18 Years - 75 Years	Beijing Shenogen Biomedical Co., Ltd
Phase I Study of Novel Estrogen Receptor(ER) a36 Modifier Icaritin in Advanced Breast Cancer Patients	NCT01278810	Metastatic Brea...	Icaritin	18 Years - 65 Years	ChineseAMS
A Phase Ib Study to Assess Safety and Efficacy of Oral Icaritin in Advanced Solid Tumors	NCT02496949	Solid Tumors	Icaritin	18 Years - 65 Years	ChineseAMS
Phase I Study of Novel Estrogen Receptor(ER) a36 Modifier Icaritin in Advanced Breast Cancer Patients	NCT01278810	Metastatic Brea...	Icaritin	18 Years - 65 Years	ChineseAMS
The Phase III Study of Icaritin Versus Sorafenib in PD-L1 Positive Advanced Hepatocellular Carcinoma Subjects	NCT03236649	Hepatocellular ...	Icaritin Sorafenib Tosyl...	18 Years - 75 Years	Beijing Shenogen Biomedical Co., Ltd
A Phase Ib Study to Assess Safety and Efficacy of Oral Icaritin in Advanced Solid Tumors	NCT02496949	Solid Tumors	Icaritin	18 Years - 65 Years	ChineseAMS
The Phase II Study of Icaritin in Patients With Advanced Hepatocellular Carcinoma	NCT01972672	Hepatocellular ...	Icaritin	18 Years - 75 Years	Beijing Shenogen Biomedical Co., Ltd
Icaritin Soft Capsule Versus Huachansu Tablet in the First-line Treatment of Unresectable Hepatocellular Carcinoma With Poor Conditions and Biomarker Enrichment (Biomarker Enrichment Study of Poor Prognosis HCC Patients, BESTPOP)	NCT05594927	Hepatocellular ...	Icaritin Huachansu	18 Years -	Beijing Shenogen Biomedical Co., Ltd

Spots Global Cancer Trial Database for icaritin

Every month we try and update this database with for icaritin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for icaritin

Every month we try and update this database with for icaritin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for icaritin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.