Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Carcinoma, Ductal

Carcinoma, Ductal, Breast

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Adenocarcinoma

Huaier Granule: oral administration, 20g each time, 3 times a day. The starting time of Huaier granule: from the beginning of adjuvant therapy to the end of adjuvant therapy, and within 60 days after the end of adjuvant therapy is also acceptable.

Conventional Treatment/visit：The postoperative adjuvant therapy and visit of TNBC are based on clinical routine.

Conventional Treatment/visit：The postoperative adjuvant therapy and visit of TNBC are based on clinical routine.

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.

Huaier Granule

Zhimin Shao, PhD

Liang Huang, PhD

Jingjie Zhang

Xiaopeng Ma

Xiang Wang

Guobing Yin

Xia Chen

Qianjun Chen

Kun Wang

Cuizhi Geng

Yi Zhou

Hui Liu

Yaojun Feng

Yi Tu

Xingrui Li

Tao Huang

Gaosong Wu

Dongfang Li

Enxiang Zhou

Chang Yao

Shui Wang

Yongzhong Yao

Jianxia Liu

Deyuan Fu

Yan Zhang

Daqing Jiang

Qifeng Yang

Haibo Wang

Sheng Liu

Shuqun Zhang

Peifen Fu

Yiding Chen

Xujun Li

Weizhu Wu

Ouchen Wang

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.

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.

Effect of Huaier Granule on Adjuvant Treatment for High-risk Early-stage Triple-negative Breast Cancer

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

Disease-free survival (DFS)：The time from randomization until the date of the first occurrence of one of the following events: recurrence of ipsilateral invasive breast tumor, local recurrence, distant metastasis, death from any cause, contralateral invasive breast cancer, ipsilateral ductal carcinoma in situ, contralateral ductal carcinoma in situ, second primary invasive carcinoma (except breast cancer).

3-year rates of disease-free survival: The percentage of participants who have not occurred events described in the DFS definition within 3 years.

Overall survival (OS): The time from randomization until the date of death from any cause.

3-year rates of overall survival: The percentage of participants who have not died from any cause within 3 years.

Invasive-disease-free survival (iDFS): The time from randomization until the date of the first occurrence of one of the following events: recurrence of ipsilateral invasive breast tumor, local recurrence, distant metastasis, death from any cause, contralateral invasive breast cancer, second primary invasive carcinoma (except breast cancer).

3-year rates of invasive-disease-free survival: The percentage of participants who have not occurred events described in the iDFS definition within 3 years.

5-year rates of disease-free survival: The percentage of participants who have not occurred events described in the DFS definition within 5 years.

5-year rates of overall survival: The percentage of participants who have not died from any cause within 5 years.

5-year rates of invasive-disease-free survival: The percentage of participants who have not occurred events described in the iDFS definition within 5 years.

Quality of Life (QOL) will be measured by European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). The scope of each domain is 0 to 100. Higher scores in the functional and general health areas indicate better functional status and quality of life, and higher scores in the symptomatic areas indicate more symptoms or problems (poorer quality of life).

AE: Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

SAE: A serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. A SADR is a serious ADR according to the above criteria of SAE. A SUSAR is an unexpected SADR.

LinkDoc Technology (Beijing) Co. Ltd.

Huazhong University of Science and Technology

Fudan University

Professor

Central Nervous System Depressants

All Drugs and Chemicals

Antipyretics

Analgesics

Anesthetics

Acetaminophen

Anesthetics, Local

Participants in this arm will receive cryoablation of their breast tumor two weeks before their routine lumpectomy. They will undergo two blood draws: one before cryoablation (at the time of consent) and one after cryoablation (at the time of surgery).

Participants in this arm will undergo a blood draw at the time of consent and then will continue with their scheduled lumpectomy (standard of care).

Cryoablation is a non-surgical, minimally invasive freezing procedure used to destroy tumors. In the breast, cryoablation is performed under ultrasound guidance. Due to the analgesic properties of freezing, no IV sedation or anesthesia is required. After administration of local anesthetic, the physician makes a 2-3 mm incision and inserts needle-like cryoprobes into the tumor, commencing a number of freeze-thaw cycles. Then the probe is removed, pressure is applied to the area, and a bandage is placed. The patient leaves the office without stitches and minimal, if any, pain. Any residual pain after the procedure is routinely treated with over the counter analgesics such as acetaminophen.

Cryoablation

Cesar Santa-Maria, MD

This study will investigate the safety, feasibility, and immune response associated with cryoablation of early invasive breast cancer prior to lumpectomy. Based on mouse models, the investigators believe that cryoablation will initiate a stronger immune response relative to the control group.

Consenting patients will be randomized to one of two arms: standard of care (control) or cryoablation (intervention). Participants will undergo a blood draw at the time of consent. Those in the control arm will continue with their standard of care lumpectomy. The intervention arm will receive cryoablation 2 weeks before their scheduled lumpectomy and undergo a second blood draw before the lumpectomy.

Pilot Study to Define the Immune Response Following Cryoablation of Invasive Breast Cancer

Assessed via phone call with participant and including any participant-reported adverse events, such as pain, bruising, bleeding, swelling, and skin changes

Immunohistochemical analysis of biomarkers in blood and resected tissue

Change in appearance based on distortion and volume loss of the breast

Assessment of whether excised tumor's margins are positive or negative for cancer, and whether re-excision is required

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participants will have unicentric pathological stage I invasive ductal breast cancer or Grade 1 or 2 DCIS measuring \<3cm in longest diameter on pathology and/or mammogram that is histologically confirmed at MSKCC.

Treatment will consist of APBI delivered using external beam RT techniques to a dose of 24 Gy in 3 fractions of 8.0 Gy delivered on consecutive weekdays

Accelerated Partial Breast Irradiation

Atif J Khan, MD

Simon Powell, MD, PhD

Philip Gilbo, MD

Joseph Panoff, MD

The purpose of this study is to determine if the dose of radiation therapy that is effective in producing a treatment response, delivered over a shorter treatment period, is a safe approach that causes few or mild side effects in women with newly diagnosed breast cancer or DCIS who have had a lumpectomy procedure.

Study of 3-Day Partial Breast Radiation Therapy in Women With Breast Cancer

Ultra-Short External Beam-Based Accelerated Partial Breast Irradiation (APBI): A Phase II Toxicity Study Nested With a Non-inferiority Assessment of APBI in New Patient Cohorts

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The study is deemed too toxic if the rate of serious toxicity is \>/= 10%.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of Huaier Granule on Adjuvant Treatment for High-risk Early-stage Triple-negative Breast Cancer	NCT04790305	Carcinoma Breas... Triple-negative... Invasive Ductal...	Huaier Granule	18 Years - 70 Years	Fudan University
Pilot Study to Define the Immune Response Following Cryoablation of Invasive Breast Cancer	NCT03523299	Invasive Ductal...	Cryoablation	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study of 3-Day Partial Breast Radiation Therapy in Women With Breast Cancer	NCT04084730	Invasive Ductal... Invasive Ductal... DCIS DCIS Grade 1 DCIS Grade 2 Breast Cancer	Accelerated Par...	45 Years -	Memorial Sloan Kettering Cancer Center
Pilot Study to Define the Immune Response Following Cryoablation of Invasive Breast Cancer	NCT03523299	Invasive Ductal...	Cryoablation	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Effect of Huaier Granule on Adjuvant Treatment for High-risk Early-stage Triple-negative Breast Cancer	NCT04790305	Carcinoma Breas... Triple-negative... Invasive Ductal...	Huaier Granule	18 Years - 70 Years	Fudan University

Spots Global Cancer Trial Database for invasive ductal carcinoma, breast