Clinical trial NCT04790305: Effect of Huaier Granule on Adjuvant Treatment for High-risk Early-stage Triple-negative Breast Cancer
Official title: Effect of Huaier Granule on Postoperative Adjuvant Treatment for High-risk Early-stage Triple-negative Invasive Ductal Carcinoma: a Prospective, Multicenter, Randomized, Controlled, Open-label Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Carcinoma Breast
Triple-negative Breast Cancer
Invasive Ductal Carcinoma, Breast
Keywords: Huaier Granule
Triple-negative Breast Cancer
Invasive Ductal Carcinoma, Breast
Adjuvant Treatment
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: LinkDoc Technology (Beijing) Co. Ltd.
name: Huazhong University of Science and Technology
First posted: 2021-03-10
Enrollment: 1072
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, multicenter, randomized, parallel controlled, open-label study. The primary purpose of this study is to evaluate the efficacy of Huaier Granule on postoperative adjuvant therapy of high-risk early-stage triple-negative invasive ductal carcinoma. The Secondary purposes are to evaluate the safety of long-term use of Huaier granules as postoperative adjuvant treatment of high-risk early-stage triple-negative invasive ductal carcinoma, and the changes of quality of life score after treatment with Huaier granule.

Detailed description: Triple-negative breast cancer（TNBC） accounts for 10% to 20% of breast cancer. TNBC is more likely to show lymph node involvement at diagnosis, and biologically more aggressive. Women with TNBC have a higher rate of distant recurrence at early-stage and a worse 5-year prognosis than women of other molecular types. Although PARP inhibitors and immune checkpoint inhibitors are showing promise to patients with advanced TNBC, however, these targeted therapies and immunotherapy for TNBC can not increase the clinical benefits of early-stage patients.

As adjuvant therapy for hepatocellular carcinoma after curative liver resection, a multicentre study demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group. Retrospective studies have shown that Huaier granules can improve the rates of disease-free survival（DFS） and overall survival（OS）, and reduce the incidence of adverse events among operable patients with TNBC.

In this study, 1072 high-risk early-stage triple-negative invasive ductal carcinoma participants (536 cases in the observation group and 536 cases in the control group) from 30 research centers will be included. The block randomization was adopted, participants will be randomly divided into the experimental group (Huaier granule plus conventional treatment/visit) and control group (conventional treatment/visit only). All participants will be followed up for 5 years, including 2-year treatment follow-up and 3-year survival follow-up. During the treatment period, the participants will be followed up every 3 months, and the survival follow-up period will be followed up every 6 months.

Eligibility criteria: Inclusion Criteria:

1. Aged from 18 to 70.
2. Histologically confirmed as breast invasive ductal carcinoma.
3. Molecular typing of breast lesions is triple-negative breast cancer, when the patient had multicentric lesions at the same time, all invasive lesions were confirmed as triple-negative.
4. Regional lymph node metastasis confirmed by postoperative pathology \[except isolated tumor cells ( ITC )\], or tumor response did not achieve pathological complete response (pCR) after neoadjuvant therapy \[neoadjuvant chemotherapy completed at least four cycles, the breast has residual invasive cancer or axillary lymph node metastasis ( except isolated tumor cells ) .\]
5. There was no local recurrence and distant metastasis of the tumor.
6. The time of randomization is during the postoperative adjuvant therapy or within 60 days after the end of the last postoperative adjuvant therapy.
7. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1.
8. Hepatic function and renal function: serum creatinine level ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) concentration / alanine aminotransferase (ALT) concentration≤ 2.5 × ULN，total serum bilirubin concentration≤ 1.5 × ULN.
9. Blood routine: neutrophil count ≥ 1.5\*109 / L, platelet count ≥ 100\*109 / L, hemoglobin concentration ≥ 90 g / L (without transfusion).
10. The participants volunteered to join the study with good compliance and signed an informed consent form.

Exclusion Criteria:

1. Bilateral breast cancer.
2. Complicated with severe cardiopathy, hepatopathy, nephropathy, endocrine system diseases. According to the researchers' judgement, the comorbidities can cause unacceptable safety risks and affect participants' compliance with research programs.
3. Suffering from malignant tumors other than breast cancer (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the past 5 years.
4. Allergic to Huaier granule.
5. Pregnant or lactating women, and those who planning a pregnancy during the study period.
6. Participating in other clinical trials or participated in other clinical studies within 3 months.
7. Patients with a poor compliance, or they are not appropriate for this study because of other reasons considered by the researchers.

Primary outcomes:
measure: 3-year rates of disease-free survival
timeFrame: Start of treatment until 3-year follow-up
Secondary outcomes:
measure: 3-year rates of overall survival
timeFrame: Start of treatment until 3-year follow-up
measure: 3-year rates of invasive-disease-free survival
timeFrame: Start of treatment until 3-year follow-up
measure: 5-year rates of disease-free survival
timeFrame: Start of treatment until 5-year follow-up
measure: 5-year rates of overall survival
timeFrame: Start of treatment until 5-year follow-up
measure: 5-year rates of invasive-disease-free survival
timeFrame: Start of treatment until 5-year follow-up
measure: Changes in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire
timeFrame: Up to 5 years since the start of treatment
measure: Incidence and severity of AE or SAE
timeFrame: Start of treatment until 3 year after enrollment
measure: Incidence and severity of ADR，SUSAR or SADR
timeFrame: Start of treatment until 3 year after enrollment
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC, Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science
state: Beijing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial Hospital of Traditional Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Shijia Zhuang
country: China
facility: The Fourth Hospital of Hebei Medical University, Hebei Tumor Hospital
state: Hebei
city: Ha'erbin
country: China
facility: The First Affiliates Hospital of Ha'erbin University
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Tongji Medical College of HUST
state: Hubei
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong Univeristy of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital of Chinese Medicine
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Provincial Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Chang chun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: LongHua Hospital Shanghai University of Traditional Chinese Medicine
state: Shanghai
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital)
state: Shanxi
city: Hangzhou
country: China
facility: The First Affiliatied Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang Univerisity of Medicine
state: Zhejiang
city: Ningbo
country: China
facility: Huamei Hospital, University of Chinese Academy of Sciences
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Medical Center Lihuili Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First School of Medicine, School of Information and Engineering,the First Affiliated Hospital of WMU
state: Zhejiang
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan University
name: Zhimin Shao, PhD
role: PRINCIPAL_INVESTIGATOR
References: