The Phase III Study of Icaritin Versus HUACHANSU PIAN in Hepatocellular Carcinoma Subjects
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|ClinicalTrials.gov Identifier: NCT03236636|
Recruitment Status : Recruiting
First Posted : August 2, 2017
Last Update Posted : January 27, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced HBV-Related Hepatocellular Carcinoma (HCC)||Drug: Icaritin Drug: HUACHANSU PIAN||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||312 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||multicenter, randomized, double-blind, double-dummy, adaptive enrichment design|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||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|
|Actual Study Start Date :||September 8, 2017|
|Estimated Primary Completion Date :||December 30, 2022|
|Estimated Study Completion Date :||December 30, 2022|
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：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.
Other Name: SNG-162
Active Comparator: HUACHANSU PIAN
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.
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.
Other Name: HUACHANSU PIAN（999）
- Overall survival (OS) [ Time Frame: 2-4 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.
- Progression-free survival (PFS) [ Time Frame: 2-3 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.
- Time to progress（TTP） [ Time Frame: 2-3 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.
- Overall response rate (ORR) [ Time Frame: 2-3 years ]ORR is defined as the proportion of subjects achieving optimal overall efficacy such as CR or partial remission (PR).
- Overall disease control rate (DCR) [ Time Frame: 2-3 years ]DCR is defined as the proportion of subjects achieving optimal overall efficacy such as CR, PR or stable disease (SD).
- Assessment on Quality of life 1 [ Time Frame: 2-4 years ]Quality of life (QOL) changes: Quality of life scores are assessed with EORTC QLQ-C30 and compared with baseline values.
- Assessment on Quality of life 2 [ Time Frame: 2-4 years ]Quality of life (QOL) changes: Quality of life scores are assessed with EORTCQLQ-HCC-18 and compared with baseline values.
- Biomarker analysis of proteome level (Immunohistochemical method) [ Time Frame: 2-4 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.
- Genome level (DNA, mRNA, miRNA) biomarker analysis [ Time Frame: 2-4 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03236636
|Contact: Yan Sun, MD||+86 10 firstname.lastname@example.org|
|Contact: Shukui Qin||+86 25 email@example.com|
|Principal Investigator:||Yan Sun, MD||Cancer Institute and Hospital, Chinese Academy of Medical Sciences|
|Principal Investigator:||Shukui Qin||NanJing PLA 81 Hospital|