Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients

Effect and Safety of Huaier Granule Versus SOX Regimen for the Prevention of Recurrence/Metastasis After Radical Surgery for Stage II-III Gastric Cancer Patients: a Prospective, Multi-center, Open-label and Randomised Control Study

This is a prospective, multi-center, open-label, randomised controlled study. The purpose of this study is to evaluate the efficacy and safety of Huaier Granule versus SOX regimen in the postoperative adjuvant treatment of resectable stage II-III gastric cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Tegafur, Gimeracil and Oteracil Potassium; Drug: Huaier granule

Detailed Description

Gastric cancer (GC) is the second most frequently diagnosed cancer and the second leading cause of cancer related deaths in China. China has a higher mortality/incidence ratio (0.845). For stage II-III GC patients, the current standard treatment is D2 gastrectomy followed by adjuvant chemotherapy. Studies showed the 5-year survival rate of early GC is nearly 95%, while the 1-year recurrence and metastasis rate after surgery is about 50%, and the rate of 2-year is as high as 70%.

Although adjuvant chemotherapy can prevent recurrence, it is inevitable to the appearance of toxic and side effects, which seriously affect the prognosis and quality of life.

Traditional Chinese medicine plays a unique role in enhancement of immune function, detoxification, and synergism of chemoradiotherapy. Huaier granule is an extract from a medicinal fungus. Previous studies have shown that Huaier granule can inhibit the proliferation, angiogenesis, metastasis and invasion of cancer cells, and can reverse the resistance of targeted drugs. Previous studies demonstrated Huaier granule is benefit to resistance to recurrence and metastasis, prolongation of patients' survival, and improvement of quality of life.

In this study, about 30 research centers will participate. Total of 702 participants will be divided into two groups (the Huaier group and the control group) at a ratio of 1:1. The Huaier group will receive Huaier granule as postoperative adjuvant therapy, and the control group will receive SOX regimen. The planned length of patient recruitment enrolment will be 2 years and the total length of visits be 3 years. After enrollment, participants will be visited every 12 weeks (window period ± 14 days) until the end of the study or until the patient withdraws from the study for any reason or dies.

• Study Type: Interventional
• Enrollment (Estimated): 702
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kaixiong Tao, PhD; Phone Number: 13507155452; Email: taokaixiong@hust.edu.cn
• Study Contact Backup: Name: Yuping Yin, PhD; Phone Number: 15927412321; Email: yinyuping2017@hust.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital
      • Contact: Kaixiong Tao, PhD; Phone Number: 13507155452; Email: taokaixiong@hust.edu.cn
      • Contact: Yuping Yin, PhD; Phone Number: 15927412321; Email: yinyuping2017@hust.edu.cn
  • Shandong
    • Qingdao, Shandong, China
      • The Affiliated Hospital of Qingdao University
      • Contact: Yanbing Zhou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Adult patients who pathologically diagnosed as stage II or III gastric adenocarcinoma and received radical surgery within 2 months prior to enrolment, and not received adjuvant treatment will be included.

Description

Inclusion Criteria:

• 18-75 years
• Pathologically diagnosed as stage II or III gastric adenocarcinoma (including gastroesophageal junction).
• Receiving radical surgery (R0, D2 resection, more than 16 lymph nodes should be detected) for gastric adenocarcinoma within 2 months prior to enrollment, and not receiving adjuvant treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status from 0 to 2.
• Patients are volunteers, have signed informed consent, and agree to cooperate with investigators in data collection.

Exclusion Criteria:

• Patients had received neoadjuvant therapy.
• Patients who have received or plan to receive targeted therapy and/or immunotherapy。
• Patients allergic to the components of Huaier granules, or avoid to use Huaier granules or use with caution.
• More than two active primary tumors at the same time.
• Patients have not recovered from surgical complications after radical surgery.
• Patients received other Chinese patent medicine with anti-tumor effects.(including but not limited to Huaier Granule, Fufangbanmao Capsule, Huachansu Capsule, Kangai Injection, Pingxiao Table) in the past 1 month.
• Not able to take medication orally cause by difficulty in swallowing, complete or incomplete gastrointestinal obstruction, active bleeding from the gastrointestinal tract, perforation, etc.
• Pregnant or lactating women or women prepare for pregnancy.
• Serious concomitant infection disease.
• Patients with severe psychiatric illness or otherwise diseases are unsuitable for this study according to the judgment by investigators.
• Patients with combined immune disease and receiving immunosuppressive therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Huaier group; The participants volunteering to take Huaier granule will be assigned to the Huaier group.	Drug: Huaier granule; Huaier granule, oral administration, 10g each time, 3 times a day. Continuous medication until disease progression, the end of the study, intolerable toxicity, withdrawal from the study for any reason or death, or until the researcher determines that the participants will no longer benefit, whichever occurs first. After disease progression, whether to continue the medication or not should be determined by the researcher and participant together. Participants will start taking Huaier granule within 1 to 3 weeks after surgery.; Other Names: Z20000109
Active Comparator: Control group; The participants volunteering to take SOX will be assigned to the control group.	Drug: Oxaliplatin; Participants will receive intravenous infusion of 130 mg/m² oxaliplatin on the first day of treatment cycle.; Drug: Tegafur, Gimeracil and Oteracil Potassium; Participants will receive oral Tegafur, Gimeracil and Oteracil Potassium (40 mg/m², twice a day) for 2 weeks, followed by 1 week of rest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year DFS rate	The proportion of patients who does not have recurrence of primary cancer, new gastric cancer, distant metastases (assessed by each investigator), or death from any cause within 3 years after receiving surgery.	up to 36-months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1, 2-year DFS rate	The proportion of patients who do not have recurrence of primary cancer, new gastric cancer, distant metastases (assessed by each investigator), or death from any cause within 1/2 years after receiving surgery.	up to 12/24-months follow-up
1, 2, 3-year OS rate	The proportion of patients who will be alive within 1/2/3 years after receiving surgery.	up to 12/24/36-months follow-up
Quality of life score	The patients will evaluated by the Short-Form 36 (SF-36) Health Survey (Chinese version), which is a 36-item questionnaire measures health on 8 multi-item dimensions. Scores are computed for each dimension by adding the recorded item responses together and transforming the results onto a scale from 0 (worst health on scale) to 100 (best health on scale).	Up to 36 months since the start of treatment
Incidence and severity of adverse events and serious adverse events	The incidence of adverse events and serious adverse events (referring to CTCAE 5.0 ) will be analyzed.	up to 36-months follow-up
Incidence and severity of adverse reactions, serious adverse reactions, suspicious and unexpected serious adverse reactions	The incidence of ADR, SADR and SUSAR (referring to CTCAE 5.0 ) will be analyzed.	up to 36-months follow-up
1, 2, 3-year local recurrence-free survival rate	The proportion of patients who do not have local recurrence or regional lymph node metastasis from an cause within 1/2/3 years after receiving surgery.	up to 12/24/36-months follow-up
1, 2, 3-year distant metastasis-free survival rate	The proportion of patients who do not have distant metastasis from an cause within 1/2/3 years after receiving surgery.	up to 12/24/36-months follow-up

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Collaborators: LinkDoc Technology (Beijing) Co. Ltd.
• Investigators: Principal Investigator: Kaixiong Tao, PhD, Wuhan Union Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: August 7, 2022
• First Submitted That Met QC Criteria: August 11, 2022
• First Posted (Actual): August 12, 2022

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: June 20, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Gastric cancer; SOX; Adjuvant therapy; Huaier granule
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Oxaliplatin; Tegafur
• Other Study ID Numbers: HE-202205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This will be discussed by researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No