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Hepatocellular Carcinoma (HCC)Phase 3NCT03236649

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

A Phase 3 study testing Icaritin and Sorafenib Tosylate Tablets in people with Hepatocellular Carcinoma (HCC), run by Beijing Shenogen Biomedical Co., Ltd at 26 sites in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hepatocellular Carcinoma (HCC)
What is being tested?
Icaritin and Sorafenib Tosylate Tablets
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
89 participants
Where
26 sitesChina
Study dates
20 Sep 2017to 8 Feb 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients who meet any of the following criteria are not allowed to enter the test:
  • Aged between 18 and 75 years old, no gender restriction;
  • 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;
  • 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.;
  • 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;
  • 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;
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  • 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;
  • The Child-Pugh score of liver function is grade A or better grade B (score≤7);
  • The ECOG score of physical condition is 0-1;
  • Expected survival time≥12 weeks;
  • 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.
  • 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;
  • 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;
  • 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);
  • Patients volunteered to join the study, sign the informed consent, have good compliance and cooperate with follow-up;
  • 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.

Who cannot join

  • Patients who meet any of the following criteria are not allowed to enter the test:
  • 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;
  • Middle or higher ascites which is clinically significant, it requires therapeutic abdominal paracentesis /drainage, or the Child-Pugh score > 2;
  • Local anticancer therapy (including surgery, ablation, hepatic arterial chemotherapy, embolization or radiotherapy) or major surgery was performed 28 days prior to randomization;
  • 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;
  • Pregnant or lactating women;
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  • 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.
  • Allograft transplants including liver transplantation were performed previously, or a liver transplant was planned during the trial;
  • Hepatic encephalopathy and / or hepatic nephropathy occurred within 6 months;
  • Patient with active hepatitis C, that is, anti -HCV positive or HCV-RNA positive and abnormal liver function;
  • Human immunodeficiency virus (HIV) tests are positive or severe infection requiring systemic treatment with antibiotics;
  • Inability to swallow, chronic diarrhea or intestinal obstruction that significantly affecting medication intake and absorption;
  • 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;
  • The patient has or is suspected to have known active autoimmune disease;
  • 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;
  • Abnormal coagulation function: prothrombin time (PT) >16S or international normalized ratio (INR) >1.5;
  • There is a history of schizophrenia or psychotropic substance abuse;
  • Known to be allergic or intolerant to Icaritin or sorafenib and excipients;
  • Other conditions that researchers believe discourage patients from participating in trials.

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

China26 sites

  • Beijing Hospital

    Beijing, Beijing Municipality

  • Cancer institute & hospital, chinese academy of medical sciences

    Beijing, Beijing Municipality

  • Chinese PLA General Hospital

    Beijing, Beijing Municipality

  • Guang'anmen Hospital of China Academy of Chinese Medical Sciences

    Beijing, Beijing Municipality

  • Peking University Cancer Hospital

    Beijing, Beijing Municipality

  • The fifth medical center of PLA General Hospital

    Beijing, Beijing Municipality

  • First Affiliated Hospital Bengbu Medical College

    Bengbu, Anhui

  • First Hospital of Jilin University

    Changchun, Jilin

  • Jilin Cancer Hospital

    Changchun, Jilin

  • Hunan Cancer Hospital

    Changsha, Hunan

  • The First People's Hospital of Foshan

    Foshan, Guangdong

  • Nanfang Hospital of Southern Medical University

    Guangzhou

  • First Affiliated Hospital of Harbin Medical University

    Harbin, Heilongjiang

  • Anhui Provincial Hospital

    Hefei, Anhui

  • The First Affiliated Hospital of Anhui Medical University

    Hefei, Anhui

  • Jinan Central Hospital

    Jinan, Shandong

  • Linyi Tumour Hospital

    Linyi, Shandong

  • Eastern Theater General Hospital,QinHuai District Medical Area

    Nanjing, Jiangsu, 210002

  • The First Affiliated Hospital with Nanjing Medical University

    Nanjing, Jiangsu

  • The Affiliated Tumor Hospital of Nantong University

    Nantong, Jiangsu

  • Fudan University Affiliated Zhongshan Hospital

    Shanghai, Shanghai Municipality

  • Peking University Shenzhen Hospital

    Shenzhen, Guangdong

  • The First Affiliated Hospital of Soochow University

    Suzhou, Jiangsu

  • Tianjin Medical University Cancer Institution & Hospital

    Tianjin, Tianjin Municipality

  • Tongji Hospital

    Wuhan, Hubei

  • Henan Cancer Hospital

    Zhengzhou, Henan

Other trials in China

About this study

Official title: 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.

Read the 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.

Being tested
Icaritin, Sorafenib Tosylate Tablets
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IcaritinDrug

    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.

  • Sorafenib Tosylate TabletsDrug

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

Study groups in NCT03236649
Study groupRoleWhat they receive
IcaritinExperimental600mg/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.
Receives: Drug: Icaritin
Sorafenib Tosylate TabletsActive comparator400mg/time, 2 tablets/time(2×200mg/tablet), 2times/day(Fasting), take orally, continuous administration until reach the standard of termination.
Receives: Drug: Sorafenib Tosylate Tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival (OS)

    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.

    Measured: 1-2 years

Secondary outcomes (6)

  1. Progression-free survival (PFS)

    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.

    Measured: 1-2 years

  2. Time to progress（TTP）

    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.

    Measured: 1-2 years

  3. Overall response rate (ORR)

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

    Measured: 1-2 years

  4. Overall disease control rate (DCR)

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

    Measured: 1-2 years

  5. Assessment on Quality of life 1

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

    Measured: 1-2 years

  6. Assessment on Quality of life 2

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

    Measured: 1-2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2017
  2. Study start20 Sep 2017
  3. Primary completion8 Feb 2022
  4. Study completion8 Feb 2022

Why it stopped: Because the clinical development plan has been changed.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Open, randomized controlled, multicenter
Masking
None (open label)
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03236649
Sponsor's protocol ID
SNG1705ICR-2
Status last verified
Jan 2021
First submitted
26 Jul 2017
Last updated
8 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Icaritin and Sorafenib Tosylate Tablets in people with Hepatocellular Carcinoma (HCC), run by Beijing Shenogen Biomedical Co., Ltd at 26 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Because the clinical development plan has been changed.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (OS) (time frame: 1-2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03236649.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.

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