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

February 7, 2023 updated by: Beijing Shenogen Biomedical Co., Ltd

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
89

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
      • Guangzhou, China
        • Nanfang Hospital of Southern Medical University
    • Anhui
      • Bengbu, Anhui, China
        • First Affiliated Hospital Bengbu Medical College
      • Hefei, Anhui, China
        • Anhui Provincial Hospital
      • Hefei, Anhui, China
        • The First Affiliated Hospital of Anhui Medical University
    • Beijing
      • Beijing, Beijing, China
        • Chinese PLA General Hospital
      • Beijing, Beijing, China
        • Beijing Hospital
      • Beijing, Beijing, China
        • Peking University Cancer Hospital
      • Beijing, Beijing, China
        • Guang'anmen Hospital of China Academy of Chinese Medical Sciences
      • Beijing, Beijing, China
        • Cancer Institute & Hospital, Chinese Academy of Medical Sciences
      • Beijing, Beijing, China
        • The Fifth Medical Center of PLA General Hospital
    • Guangdong
      • Foshan, Guangdong, China
        • The First People's Hospital of Foshan
      • Shenzhen, Guangdong, China
        • Peking University Shenzhen Hospital
    • Heilongjiang
      • Ha'erbin, Heilongjiang, China
        • First Affiliated Hospital of Harbin Medical University
    • Henan
      • Zhengzhou, Henan, China
        • Henan Cancer Hospital
    • Hubei
      • Wuhan, Hubei, China
        • Tongji Hospital
    • Hunan
      • Changsha, Hunan, China
        • Hunan Cancer Hospital
    • Jiangsu
      • Nanjing, Jiangsu, China
        • The First Affiliated Hospital with Nanjing Medical University
      • Nanjing, Jiangsu, China, 210002
        • Eastern Theater General Hospital,QinHuai District Medical Area
      • Nantong, Jiangsu, China
        • The Affiliated Tumor Hospital of Nantong University
      • Suzhou, Jiangsu, China
        • The First Affiliated Hospital of Soochow University
    • Jilin
      • Changchun, Jilin, China
        • Jilin Cancer Hospital
      • Changchun, Jilin, China
        • First Hospital of Jilin University
    • Shandong
      • Jinan, Shandong, China
        • Jinan Central Hospital
      • Linyi, Shandong, China
        • Linyi Tumour Hospital
    • Shanghai
      • Shanghai, Shanghai, China
        • Fudan University Affiliated Zhongshan Hospital
    • Tianjin
      • Tianjin, Tianjin, China
        • Tianjin Medical University Cancer Institution & Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients who meet any of the following criteria are not allowed to enter the test:

    1. Aged between 18 and 75 years old, no gender restriction;
    2. According to "Primary Liver Cancer Diagnosis and Treatment Standard." (2011 Edition) issued by the National Health and Family Planning Commission, advanced or metastatic hepatocellular carcinoma patients who diagnosed by pathology /cytology fail to undergo liver surgery and/or other local treatment (ablation or hepatic artery intervention), or have recurrence and progression after surgery and/or other local treatment;
    3. Not previously accepted first-line system therapy (systemic chemotherapy, molecular targeting, immunotherapy and research medication, etc.) for advanced or metastatic HCC, including but not limited to systematic chemotherapy with oxaliplatin, sorafenib, PD-1/PD-L1 antibody and Icaritin, etc.;
    4. The central laboratory must receive specimen of tumor tissue (wax block or white slice) at first, and detect the PD-L1of tumor tissues by immunohistochemistry, only positive expression of PD-L1 in immune cells can be enrolled;
    5. According to the evaluation criteria of solid tumor reaction (RECIST 1.1), it has at least one measurable target lesion (Non-lymph node lesions with the longest diameter larger than 10mm, lymph node lesions with the short diameter larger than 15mm); the lesions previously received local treatment such as ablation or hepatic artery interventional therapy should be detected by computed tomography (CT) / magnetic resonance imaging (MRI) and according to RECIST1.1, It's sure that disease progression has occurred and the longest diameter is more than 1.0cm,it can be used as a measurable target lesions;
    6. Liver surgery was performed more than 3 months ago, ablation or interventional treatment of hepatic artery was performed more than 4 weeks ago, and the adverse reactions returned to normal; After surgery or other local treatment, if patients have gone beyond the norm for systemic adjuvant chemotherapy or sorafenib, it will need more than 6 months after the chemotherapy or sorafenib, and disease progression and / or metastasis have occurred;
    7. The Child-Pugh score of liver function is grade A or better grade B (score≤7);
    8. The ECOG score of physical condition is 0-1;
    9. Expected survival time≥12 weeks;
    10. 2 weeks before the first medication of the trial, there is no use of modern Chinese medicine preparation with liver cancer indication, including Delisheng injection, Kanglaite injection/soft capsule, Aidi injection or Cotside injection, elemene injection/oral liquid, Huaier granule, cinobufotalin and GanFuLe capsule / tablet and so on.

    11. The function of the main organs is basically normal and meets the following requirements:

      ① Marrow: Absolute neutrophil count≥1.5×109/L, platelet≥80×109/L, hemoglobin≥90g/L;

      ② Liver: Total bilirubin≤1.5 times of the upper limit of normal(ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤5 × ULN; albumin≥29g/L;

      ③ Kidney: Serum creatinine≤ 1.5 x ULN, or creatinine clearance rate≥ 50ml/min;

    12. 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;
    13. Women of childbearing age must receive pregnancy tests 14 days before treatment and the results are negative; Men and women must take effective contraceptive measures during the trial (from signing an informed consent to 3 months after the last medication);
    14. Patients volunteered to join the study, sign the informed consent, have good compliance and cooperate with follow-up;
    15. 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 or at the same time, there were other cancers whose primary site or histology are entirely different from hepatocellular carcinoma, except cervical carcinoma in situ, previously treated basal cell carcinoma and superficial bladder tumor (Ta, Tis, T1); Patients with other malignancies who have been cured for >5 years prior to enrollment may be admitted to the group;
    5. Pregnant or lactating women;
    6. Patients who have high blood pressure and failed to receive good control with antihypertensive drugs (systolic blood pressure >140mmHg, diastolic pressure >100mmHg); Patients suffer from CTCAE classification type II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmia; and/or New York Heart Association(NYHA) grade 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;
    10. Human immunodeficiency virus (HIV) tests are positive or severe infection requiring systemic treatment with antibiotics;
    11. Inability to swallow, chronic diarrhea or intestinal obstruction that significantly affecting medication intake and absorption;
    12. Having a history of digestive tract bleeding within 6 months, or with a clear gastrointestinal bleeding tendency, including local active ulcerative lesions, positive fecal occult blood;
    13. The patient has or is suspected to have known active autoimmune disease;
    14. If a central nervous system metastasis is known and a metastasis of the central nervous system is suspected, the cranial MRI examination should be performed to exclude it;
    15. Abnormal coagulation function: prothrombin time (PT) >16S or international normalized ratio (INR) >1.5;
    16. There is a history of schizophrenia or psychotropic substance abuse;
    17. Known to be allergic or intolerant to Icaritin or sorafenib and excipients;
    18. Other conditions that researchers believe discourage patients from participating in trials.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: 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: 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.
ACTIVE_COMPARATOR: Sorafenib Tosylate Tablets
400mg/time, 2 tablets/time(2×200mg/tablet), 2times/day(Fasting), take orally, continuous administration until reach the standard of termination.
Drug: Sorafenib Tosylate Tablets
400mg/time, 2 tablets/time(2×200mg/tablet), 2times/day(Fasting), take orally, continuous administration until reach the standard of termination.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 1-2 years
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.
1-2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 1-2 years
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.
1-2 years
Time to progress（TTP）
Time Frame: 1-2 years
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.
1-2 years
Overall response rate (ORR)
Time Frame: 1-2 years
ORR is defined as the proportion of subjects achieving optimal overall efficacy such as CR or partial remission (PR).
1-2 years
Overall disease control rate (DCR)
Time Frame: 1-2 years
DCR is defined as the proportion of subjects achieving optimal overall efficacy such as CR, PR or stable disease (SD).
1-2 years
Assessment on Quality of life 1
Time Frame: 1-2 years
Quality of life (QOL) changes: Quality of life scores are assessed with EORTC QLQ-C30 and compared with baseline values.
1-2 years
Assessment on Quality of life 2
Time Frame: 1-2 years
Quality of life (QOL) changes: Quality of life scores are assessed with EORTCQLQ-HCC-18 and compared with baseline values.
1-2 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Biomarker analysis of proteome level (Immunohistochemical method)
Time Frame: 1-2 years
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.
1-2 years
Genome level (DNA, mRNA, miRNA) biomarker analysis
Time Frame: 1-2 years
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
1-2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Beijing Shenogen Biomedical Co., Ltd

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The First Affiliated Hospital with Nanjing Medical University
General Hospital of Chinese Armed Police Forces
307 Hospital of PLA
The First Affiliated Hospital of Anhui Medical University
Fudan University
Beijing YouAn Hospital
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Chinese PLA General Hospital
Henan Cancer Hospital
Tongji Hospital
Hunan Cancer Hospital
Peking University Cancer Hospital & Institute
Jilin Provincial Tumor Hospital
Guang'anmen Hospital of China Academy of Chinese Medical Sciences
Nanfang Hospital of Southern Medical University
Tianjin Medical University Cancer Institute and Hospital
Beijing Hospital
The First Affiliated Hospital of Soochow University
The First Hospital of Jilin University
First People's Hospital of Foshan
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Jinan Central Hospital
The Fourth Hospital of Hebei Medical University
First Affiliated Hospital Bengbu Medical College
First Affiliated Hospital of Harbin Medical University
Anhui Provincial Hospital
The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China
Eastern Theater General Hospital,QinHuai District Medical Area
Linyi Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 20, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 8, 2022

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 8, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 26, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 28, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 2, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 8, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SNG1705ICR-2

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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