YIV-906 (Formerly PHY906/KD018) With Sorafenib in HBV(+) Hepatocellular Carcinoma (HCC)

  • STATUS
    Recruiting
  • End date
    Feb 28, 2022
  • participants needed
    125
  • sponsor
    Yiviva Inc.
Updated on 27 January 2021
Investigator
Shwu-huey Liu, PhD
Primary Contact
Shanghai University of Traditional Chinese Medicine Shuguang Hospital (0.0 mi away) Contact
+31 other location

Summary

The aim of this study is to compare the efficacy and safety of YIV-906 plus standard-of-care sorafenib versus those of sorafenib alone as a first-line systemic treatment for patients with Hepatitis B (+) associated advanced hepatocellular carcinoma.

YIV-906 (PHY906, KD018) is an immune system modulator. Clinical and preclinical research suggests that YIV-906 could act to enhance the body's immune response to fight cancer and increase the anti-tumor activity of sorafenib and protect and repair the gastrointestinal tract by reducing inflammation and promoting tissue regeneration.

Inspired by a 1,800-year-old traditional medicine still in use today, YIV-906 is a botanical drug candidate, composed of an extract of four herbs and administered in oral capsule form.

The CALM (Combination of YIV-906 and Sorafenib to treat Advanced Liver cancer in a Multi-center study) trial is a multi-regional, randomized, placebo-controlled study.

Description

HCC patients with chronic HBV (+) (HBsAg(+) and IgM anti-HBc (-)), and Child-Pugh A status will be randomized to either the study arm (YIV-906 plus sorafenib) or control arm (placebo plus sorafenib) at ratio of 2:1. Patients will be stratified according to metastatic status (extrahepatic/vascular invasion vs. none), and their ECOG performance status (0 vs. 1) at randomization.

  • ARM I: Patients receive Placebo + Sorafenib
  • ARM II: Patients receive YIV-906+ Sorafenib

Patients in the study arm will be treated orally each 28-day course with YIV-906 (600 mg (3 capsules) BID) + sorafenib (400 mg BID) according to the following schedule: sorafenib BID daily treatment for 28 days, and YIV-906 BID 4 days on and 3 days off weekly in each course.

All patients will be evaluated and graded for adverse events according to the NCI Common Terminology for Adverse Events, version 5.0 (CTCAE). The Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) will be used to establish disease response or progression.

Patients will be evaluated for PFS, TTP, OS, antitumor response every two cycles, and QoL and safety at the beginning of each cycle. Biomarkers are mandatory and will be studied prior to drug administration on day 1 of each cycle. Gut and oral microbiota studies as well as TCM Syndrome Research are optional.

PK is only optional in China study sites, and limited to the first 15 male and 15 female patients. Patients will be randomized to either study drug arm or placebo arm (2:1 ratio). PK studied immediately prior to dose administration and at 1 hour, 2 hours, 4 hours, and 12 hours post-dose administration on Day 1 of Cycles 1.

Details
Condition Advanced Hepatocellular Carcinoma
Treatment YIV-906+Sorafenib, Placebo+Sorafenib
Clinical Study IdentifierNCT04000737
SponsorYiviva Inc.
Last Modified on27 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Male or females 18 years old with the ability to take oral drugs
Diagnosis of advanced HCC according to the American Association for the Study of Liver Diseases (AASLD) Guidelines (Heimbach et al. 2018) or diagnosis by tissue pathology
Life expectancy of at least 3 months
Presence of chronic hepatitis B (HBsAg (+) and IgM anti-HBc (-))
Never received systemic antitumor therapy
Patients must have at least one tumor lesion that meets both of the following
criteria
Measurable disease" according to RECIST 1.1 , i.e. at least one measurable lesion
Advanced unresectable HCC that have liver limited disease who have failed or not candidates to local therapies including surgery and local-regional therapies; or patients with extrahepatic disease
Patients with an Eastern Cooperative Oncology Group (ECOG) performance status 1
Cirrhotic status of current Child-Pugh class A. Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period
For patients with positive HBV-DNA and/or positive HBsAg results, they must be treated with antivirals (per local standard of care), as prophylaxis starting at least 1-2 weeks prior to receiving study drug and willingness to continue treatment for the length of the study
Patients with adequate organ reserve, such as laboratory parameters
Absolute Neutrophil Count (ANC) 1.5 x 10^9/L
Platelets 60000 x 10^6/L
Hemoglobin (Hgb) 9 g/dL
Serum alanine amino-transferase (ALT) 5 x ULN
Adequate renal function, based upon meeting the following laboratory criteria within 7 days before randomization
Serum creatinine 1.5 x ULN or calculated creatinine clearance 40mL/min (using the Cockroft-Gault equation: (140-age) x weight (kg)/(serum creatinine x 72 [mg/dL] for males. (For females multiply by 0.85) AND
-hour urine protein <1 g
Ability to understand and willingness to sign a written informed consent and to be able to follow the visit schedule

Exclusion Criteria

Patients who ever have HCV infection
Patients who have received systemic chemo-therapies or immunotherapy or molecular target therapies
Patients who have received any local anti-cancer therapy within 4 weeks prior to Cycle 1 treatment
Active bleeding (including gastrointestinal bleeding, encephalopathy, and ascites) during the last 4 weeks prior to Cycle 1 treatment
Patients with a history of allergy to the known components of YIV-906
Known history of human immunodeficiency virus (HIV) seropositivity
Known central nervous system metastasis including brain metastasis and meningeal carcinomatosis
Hepatocholangiocarcinoma, fibrolamellar cell carcinoma and mixed hepatocellular carcinoma
Active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 5 years
Any severe and/or uncontrolled medical conditions including but not limiting to
Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction 6 months prior to Cycle 1 treatment, serious uncontrolled cardiac arrhythmia, uncontrolled hypertension
Previous transient ischemic attack (TIA), cerebral vascular accident (CVA), symptomatic peripheral vascular disease (PVD) within last 6 months of Cycle 1 treatment
Congenital long QT syndrome
Alcoholic patients
Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study therapy, in the opinion of the investigator, except chronic HBV
Impairment of gastrointestinal function or who have a gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
Patients who have had organ transplantation
Patients receiving chronic treatment with corticosteroids (except for intermittent topical or local injection or aldosterone) or other immunosuppressive agent Subjects receive any blood transfusion, albumin transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), TPO or other medical supportive treatment prior to Cycle 1 treatment
Patients treated with drugs known to be strong inducers of isoenzyme CYP3A within 7 days of Cycle 1 treatment
Patients who have undergone major surgery 2 weeks prior to starting study drug or who have not recovered from surgery
Patients who have received an investigational drug or therapy within the last 4 weeks prior to Cycle 1 treatment
Pregnant and/or breastfeeding women
Men and women of childbearing age and potential, who are not willing to use effective contraception
Unwilling or unable to follow protocol requirements or to give informed consent
An ongoing or recent history of autoimmune, uncontrolled psychiatric disorders and drug abuse
Uncontrolled hereditary or acquired thrombotic or bleeding disorder
Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection
Therapeutic dose anticoagulation with warfarin or similar agents
Chronic therapy with nonsteroidal anti-inflammatory agents or other antiplatelet agents. Aspirin at doses up to 100 milligrams/day is permitted
Patients with an estimated or calculated baseline creatinine clearance of less than 40 mL/min should not be enrolled in this trial
No patient, however, may enroll in this trial if they are taking phenytoin (Dilantin)
Patients taking traditional Chinese medicines within 14 days prior to taking first dose of study treatment
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