Effect and Safety of Adjuvant Huaier Granule Versus Standard Chemotherapy Regimens in Gastric Cancer Patients

Study Overview
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Brief Summary
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This is a prospective, multi-center, observational study. The purpose of this study is to evaluate the efficacy and safety of Huaier Granule versus standard chemotherapy regimens in the postoperative adjuvant treatment of resectable stage II-III gastric cancer.

Detailed Description
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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 20 research centers will participate. Total of 828 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 or XELOX. 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 3 months (window period ± 14 days) until the end of the study or until the patient withdraws from the study for any reason or dies.

Official Title
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Effect and Safety of Adjuvant Huaier Granule Versus Standard Chemotherapy Regimens in Resectable Stage II-III Gastric Cancer Patients: a Prospective, Multi-center, and Observational Study

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Huaier granule
* Drug: Oxaliplatin
* Drug: Tegafur, Gimeracil and Oteracil Potassium
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years Pathologically diagnosed as stage II or III gastric adenocarcinoma (not 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 allergic to the components of Huaier granules, or avoid to use Huaier granules or use with caution (Huaier Group). More than two active primary tumors at the same time. Patients have not recovered from surgical complications after radical surgery. Expected survival time is less than 3 years. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Huaier group<br>The participants volunteering to take Huaier granule will be assigned to the Huaier group. | Drug: Huaier granule<br>* Huaier granule, oral administration, 20g each time, 3 times a day. Continuous medication until the end of the study, intolerable toxicity, withdrawal from the study for any reason or death, whichever occurs first; or after researcher's judgment, participants will no longer benefit from the treatment. 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 10 days after surgery.<br>* Other names: Z20000109;|
| Control group<br>The participants volunteering to take SOX or XELOX will be assigned to the control group. | Drug: Oxaliplatin<br>* Participants will receive intravenous infusion of 130 mg/m² oxaliplatin on the first day of treatment cycle.<br>Drug: Tegafur, Gimeracil and Oteracil Potassium<br>* Participants will receive oral Tegafur, Gimeracil and Oteracil Potassium (40 mg/m², twice a day) for 2 weeks, followed by 1 week of rest.<br>Drug: Capecitabine<br>* Participants will receive oral Capecitabine (1000 mg/m², twice a day) for 2 weeks, followed by 1 week of rest.<br>|

What is the study measuring?
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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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Huaier granule, Gastric cancer, SOX, Adjuvant therapy, XELOX