Clinical trial NCT04172259: ACHP-THP vs EC-THP as Neoadjuvant Therapy for HER2-positive EBC
Official title: A Multi-center Randomized Phase II Study of Doxorubicin Liposome Versus Epirubicin Plus Cyclophosphamide Combined With Trastuzumab and Pertuzumab(HP), Followed by Taxon Plus HP as Neoadjuvant Therapy for HER2-positive Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Neoadjuvant Chemotherapy
Keywords: Human epidermal growth factor receptor 2
Pathology complete response
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital, Sun Yat-Sen University
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
First posted: 2019-11-21
Enrollment: 156
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: Breast cancer is the most common malignant tumor in women. EC-TH is one of the standard chemotherapy regimens for HER-2 positive early breast cancer(EBC). Earlier use of trastuzumab may improve DFS rate. In this study, the investigators want to find out whether ACH-TH regimen compared with the EC-TH regimen in HER2+ EBC could improve the pCR rate in neoadjuvant chemotherapy.

We update protocol in Sep 2020, because Pertuzumab is approveled by Chinese goverment and coverd by national insurance, dual target therapy with Trastuzumab and Pertuzumab is the standard therapy for neoadjuvant therapy of HER2-positive EBC patients.

Detailed description: Breast cancer is the most common malignant tumor in women. EC-TH is one of the standard chemotherapy regimens for HER-2 positive early breast cancer(EBC). Earlier use of trastuzumab could improve the DFS rate in HER2+ EBC. But due to the cardio-toxicity of both anthracycline and trastuzumab, the investigators usually avoid using these two drugs synchronously. The guidelines do not recommend ECH-TH regemin because of cardiac adverse effect. Doxorubicin liposome(A) has equivalent effect as anthracycline in advaced breast cancer(ABC), lower cardiac toxicity and could be combined use with trastuzumab. In this study, the investigators want to find out whether ACH-TH regimen compared with the EC-TH regimen in HER2+ EBC could improve the pCR rate in neoadjuvant chemotherapy.

We update protocol in Sep 2020, because Pertuzumab is approveled by Chinese goverment and coverd by national insurance, dual target therapy with Trastuzumab and Pertuzumab is the standard therapy for neoadjuvant therapy of HER2-positive EBC patients. So now we want to compare ACHP-THP regimen compared with the EC-THP regimen in HER2+ EBC could improve the pCR rate in neoadjuvant chemotherapy.

Eligibility criteria: Inclusion Criteria:

* Adult patient, \>/= 18 years of age, \</= 70 years of age.
* HER2-positive breast cancer
* Histologically confirmed invasive breast carcinoma
* Clinical stage T2-4/N0-3/M0 or node positive at presentation (patients with T1 tumors will not be eligible)
* Known hormone-receptor status
* Non previous anti-breast cancer neoadjuvant chemotherapy
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Adequate hematologic, renal and liver function
* Screening Left ventricular ejection fraction (LVEF) \>/= 50% on echocardiogram (ECHO)
* Adequate organ function

Exclusion Criteria:

* Stage IV (metastatic) breast cancer or bilateral breast cancer
* History of any prior (ipsi- or contralateral breast cancer except lobular carcinoma in situ)
* History of other malignancy within the last 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other non-breast malignancies with a similar outcome to those mentioned above
* Cardiopulmonary dysfunction as defined by protocol
* Current severe, uncontrolled systemic disease
* Pregnant or lactating women
* Any known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis
* Concurrent serious uncontrolled infections requiring treatment or known infection with HIV
* History of intolerance, including Grade 3 to 4 infusion reaction or
* hypersensitivity to trastuzumab or chemotherapy drugs

Primary outcomes:
measure: Pathological Complete Response rate (pCR)
timeFrame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug).
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Approximately 20-24 weeks from first dose of study drug
measure: Event Free Survival (EFS)
timeFrame: Up to 5 years from the date of definitive surgery
measure: Overall Survival (OS)
timeFrame: Up to 5 years from the date of definitive surgery.
measure: Incidence of chemotherapy-induced cardiotoxicity
timeFrame: Approximately 20-24 weeks from first dose of study drug
measure: Change From Baseline Between Treatment Comparison in Euro Quality of Life (EQ-5D) Index
timeFrame: First day of treatment (Day 1) up to 6 months during the post-surgery follow-up period (approximately 15 months from first dose of study drug)
measure: Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy -Breast (FACT-B)
timeFrame: First day of treatment (Day 1) up to 6 months during the post-surgery follow-up period (approximately 15 months from first dose of study drug)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: SunYat-sen University Cancer Center
name: Wen Xia, MD
role: PRINCIPAL_INVESTIGATOR
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