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

Overview

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.

Interventions

• Drug Huaier Granule
  The subjects in the experimental group will be treated with Huaier Granule continuously for 2 years or until the disease progressed, intolerable toxicity, withdrawal of informed consent form or died for any reason.

Primary outcome measures

• 3-year rates of disease-free survival [Time frame: Start of treatment until 3-year follow-up]

Secondary outcome measures (8)

• 3-year rates of overall survival [Time frame: Start of treatment until 3-year follow-up]
• 3-year rates of invasive-disease-free survival [Time frame: Start of treatment until 3-year follow-up]
• 5-year rates of disease-free survival [Time frame: Start of treatment until 5-year follow-up]
• 5-year rates of overall survival [Time frame: Start of treatment until 5-year follow-up]
• 5-year rates of invasive-disease-free survival [Time frame: Start of treatment until 5-year follow-up]
• Changes in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire [Time frame: Up to 5 years since the start of treatment]
• Incidence and severity of AE or SAE [Time frame: Start of treatment until 3 year after enrollment]
• Incidence and severity of ADR，SUSAR or SADR [Time frame: Start of treatment until 3 year after enrollment]

Eligibility criteria

Inclusion criteria

• Aged from 18 to 70.
• Histologically confirmed as breast invasive ductal carcinoma.
• 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.
• 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 \[neoadjuvant chemotherapy completed at least four cycles, the breast has residual invasive cancer or axillary lymph node metastasis ( except isolated tumor cells ) .\]
• There was no local recurrence and distant metastasis of the tumor.
• The time of randomization is during the postoperative adjuvant therapy or within 60 days after the end of the last postoperative adjuvant therapy.
• Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1.
• 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.
• Blood routine: neutrophil count ≥ 1.5\*109 / L, platelet count ≥ 100\*109 / L, hemoglobin concentration ≥ 90 g / L (without transfusion).
• The participants volunteered to join the study with good compliance and signed an informed consent form.

Exclusion criteria

• Bilateral breast cancer.
• 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.
• 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.
• Allergic to Huaier granule.
• Pregnant or lactating women, and those who planning a pregnancy during the study period.
• Participating in other clinical trials or participated in other clinical studies within 3 months.
• Patients with a poor compliance, or they are not appropriate for this study because of other reasons considered by the researchers.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 34 centers

• The First Affiliated Hospital of Anhui Medical University — Hefei
• The First Affiliated Hospital of USTC, Anhui Provincial Hospital — Hefei
• Cancer Hospital Chinese Academy of Medical Science — Beijing
• The Second Affiliated Hospital of Chongqing Medical University — Chongqing
• Fujian Cancer Hospital — Fuzhou
• Guangdong Provincial Hospital of Traditional Chinese Medicine — Guangzhou
• Guangdong Provincial People's Hospital — Guangzhou
• The Fourth Hospital of Hebei Medical University, Hebei Tumor Hospital — Shijiazhuang
• … and 26 more centers

Identifiers

NCT: NCT04790305 · HE-202012

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗