Trial Title:
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)
NCT ID:
NCT05594927
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Conditions: Keywords:
Icaritin, Poor Conditions, Composite Biomarker
First-line Treatment
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
Icaritin
Description:
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.
Arm group label:
Icaritin soft capsule
Intervention type:
Drug
Intervention name:
Huachansu
Description:
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.
Arm group label:
Huachansu tablet
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female, 18 years and older;
2. HCC patients who meet the clinical diagnostic criteria of the Chinese Diagnosis and
Treatment Guideline of Primary Liver Cancer (2022 edition), and/or with diagnosis
confirmed histopathologically/cytologically;
3. Unresectable HCC patients;
4. Patients with a peripheral blood composite biomarker Score ≥ 2 points, 1 point each
for AFP ≥ 400 ng/mL, TNF-α < 2.5 pg/mL, and IFN-γ ≥ 7.0 pg/mL ;
5. No prior first-line systemic treatment for HCC, including sorafenib, lenvatinib,
donafenib, atezolizumab plus bevacizumab, sintilimab plus a bevacizumab biosimilar,
camrelizumab plus apatinib, and durvalumab plus tremelimumab, oxaliplatin-based
systemic chemotherapy (FOLFOX4) , icaritin, huachansu, and other anti-cancer drugs
such as targeted agents, immune checkpoint inhibitors, and systemic chemotherapy;
6. Child-Pugh score ≤ 7;
7. Vital organ functions should meet the following requirements:
① Hematopoietic function: platelet ≥ 40×10^9/L, hemoglobin ≥ 80 g/L, white blood
cell ≥ 2.0×10^9/L;
② Liver function: total bilirubin ≤ 1.5 times upper limit of normal (ULN) , alanine
Aminotransferase (ALT) and aspartate Aminotransferase (AST) ≤ 5×ULN; albumin ≥ 28
g/L;
③ Renal function: Serum Creatinine ≤ 1.5×ULN, or creatinine clearance rate ≥ 50
mL/min;
8. If HBV-DNA ≥ 10^4 copies/mL (2000 IU/mL), antiviral and liver protection therapy
must be used before enrollment, until HBV-DNA < 10^4 copies/mL (2000 IU/mL). In
which case, the antiviral drugs should be administered continuously and liver
function and hepatitis B virus load will be monitored during the study period;
9. Patients who meet one of two conditions: (A) are not or less appropriate candidates
for first-line standard treatments recommended by the guidelines; (B) are not
willing to receive first-line standard treatments recommended by the guidelines.
10. Surgical resection ended > 3 months, local ablation, hepatic artery intervention or
radiotherapy ended > 4 weeks before randomization (implantation of radioactive
particles ended > 3 months) and relevant adverse reactions having recovered.
Patients without extrahepatic spread must have radiographic evidence of disease
progression after local treatment;
11. Patients who had previously received adjuvant systemic therapy after surgical
resection experienced the first radiographic disease progression more than 6 months
after withdrawal of adjuvant therapy will be eligible for enrollment;
12. Within 2 weeks prior to randomization, no treatment with modern Chinese traditional
medicine preparations with anti-tumor indications (refer to the 11th inclusion
criterion when huaier granule was used as systemic adjuvant therapy),
immunomodulators such as interferon-α and thymalfasin, tumor vaccines and cellular
immunotherapy;
13. No blood transfusion or infusion of blood products, no use of hematopoietic growth
factors (such as granulocyte colony-stimulating factor G-CSF), and no albumin
infusion within 2 weeks prior to randomization;
14. ≥1 measurable lesion according to the Response Evaluation Criteria In Solid Tumors
(RECIST 1.1), defined as a non-lymphoid lesion with the longest diameter ≥ 10 mm or
a lymph node lesion with the short axis ≥ 15 mm; a lesion after previous
radiotherapy or other loco-regional therapy which has been demonstrated progression
confirmed per RECIST v1.1 with the longest diameter ≥ 10 mm scanned by
dynamic-enhanced CT/ dynamic-enhanced MRI is to be deemed as a measurable lesion.
15. Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 or 1;
16. Expected survival of ≥ 12 weeks;
17. Female patients of childbearing age with a negative blood pregnancy within the first
7 days prior to randomization will be eligible; Female patients of childbearing age
or male patients with female sexual partners of childbearing age should take
effective contraceptive measures throughout treatment and within 3 months after the
last dose;
18. Voluntary agreement to sign informed consent and the willingness and ability to
comply with protocol schedules and testing;
19. No treatment with any other investigational drugs or medical devices within 4 weeks
prior to randomization.
Exclusion Criteria:
1. Tumor occupancy ≥ 70% of liver, or tumor thrombus occupancy ≥ 50% of the main trunk
of portal vein, or mesenteric vein or inferior vena cava tumor thrombus;
2. Moderate-to-severe ascites, i.e., the score of the indicator is > 2;
Moderate-to-severe, or symptomatic pleural effusion and pericardial effusion
requiring drainage;
3. Receipt of major surgery (craniotomy, thoracotomy, laparotomy, hip replacement,
etc.) within 28 days prior to randomization or planned to receive major surgery
during the study;
4. Other types of primary liver cancer, such as intrahepatic cholangiocarcinoma, mixed
HCC and cholangiocarcinoma, fibrolamellar HCC, etc. Other malignancies within 5
years prior to signing the informed consent form or at present, excluding radically
treated basal cell carcinoma of skin, squamous cell carcinoma of skin and/or
radically resected carcinoma in situ;
5. Pregnant or lactating women;
6. Grade 2 or above myocardial ischemia or myocardial infarction (NCI-CTCAE v5.0),
poorly-controlled arrhythmia, and/or New York Heart Association (NYHA) class III or
IV cardiac insufficiency;
7. Patients who previously received allogeneic transplantation including liver
transplantation, or plan to undergo liver transplantation during the study;
8. History of hepatic encephalopathy and/or hepatic nephropathy within 6 months prior
to signing informed consent ;
9. HCV-RNA positive, ALT and/or AST > 2×ULN;
10. Human immunodeficiency virus (HIV) antibody positive;
11. Severe infection (≥ Grade 3 of NCI-CTCAE v5.0 criteria) at randomization;
12. Unable to swallow, chronic diarrhea or intestinal obstruction, which will
significantly affect oral administration and absorption of the study drug;
13. History of gastrointestinal hemorrhage within 6 months before signing informed
consent, or with clear tendency for gastrointestinal hemorrhage at present, such as:
local active ulcers, stool occult blood ≥ 2+ or positive at two consecutive tests
(attention should be paid to exclude the influence of food, drugs and other
diseases);
14. Active autoimmune diseases requiring systemic treatment (e.g., NSAIDs,
immunosuppressants, biologics, corticosteroids, etc.) except for patients receiving
replacement therapy (e.g., hypothyroidism treated with thyroxine, type 1 diabetes
mellitus treated with insulin, adrenal or pituitary insufficiency treated with
physiologic corticosteroids, etc.);
15. Known central nervous system (CNS) metastasis; patients suspected of CNS metastasis
need to undergo cerebral MRI/CT for exclusion;
16. Significant coagulation function abnormalities: international standardized ratio
(INR) > 1.5 or prothrombin time (PT) > 16 s;
17. History of schizophrenia or psychiatric drug abuse;
18. Known allergy or intolerance to any ingredients of icaritin or huachansu
preparations;
19. Other conditions that the investigator considers inappropriate for participation in
this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Second Affiliated Hospital of Nanchang University
Address:
City:
Nanchang
Zip:
330006
Country:
China
Status:
Recruiting
Contact:
Last name:
JianBin Wu, Doctor
Phone:
0791-86300985
Email:
585482997@qq.com
Facility:
Name:
Chifeng Municipal Hospital
Address:
City:
Chifeng
Country:
China
Status:
Recruiting
Contact:
Last name:
Hongbo Ji, Doctor
Phone:
0476-8231279
Email:
2060255120@qq.com
Facility:
Name:
Tianjin Medical University Cancer Institute & Hospital
Address:
City:
Tianjin
Zip:
300060
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jihui Hao, MD
Phone:
022-23340123
Email:
haojihui@tjmuch.com
Start date:
December 12, 2022
Completion date:
August 30, 2025
Lead sponsor:
Agency:
Beijing Shenogen Biomedical Co., Ltd
Agency class:
Industry
Source:
Beijing Shenogen Biomedical Co., Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05594927
