ACH-TH vs EC-TH as Neoadjuvant Therapy for HER2-positive EBC

Sponsor

Sun Yat-sen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT04172259

Collaborator

First Affiliated Hospital, Sun Yat-Sen University (Other), Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Other)

180

Enrollment

Location

Arms

35.7

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Neoadjuvant Chemotherapy	Drug: Doxorubicin liposome Drug: Cyclophosphamide Drug: Trastuzumab Drug: Docetaxel Drug: Epirubicin	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multi-center Randomized Phase II Study of Doxorubicin Liposome Versus Epirubicin Plus Cyclophosphamide Combined With Trastuzumab, Followed by Docetaxel Plus Trastuzumab as Neoadjuvant Therapy for HER2-positive Early Breast Cancer

Actual Study Start Date :

Jan 10, 2019

Anticipated Primary Completion Date :

Apr 1, 2021

Anticipated Study Completion Date :

Jan 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ACH-TH Doxorubicin liposome（PLD）35 mg/m2 Cyclophosphamide（CTX）600 mg/m2 Trastuzumab：first cycle 8mg/kg，then 6mg/kg Docetaxel（DOC）75 mg/m2 every 3 weeks	Drug: Doxorubicin liposome PLD Other Names: PLD Drug: Cyclophosphamide CTX Other Names: CTX Drug: Trastuzumab H Other Names: Herceptin Drug: Docetaxel DOC Other Names: Taxotere
Active Comparator: EC-TH Epirubicin（EPI）90 mg/m2 Cyclophosphamide（CTX）600 mg/m2 Trastuzumab：first cycle 8mg/kg，then 6mg/kg Docetaxel（DOC）75 mg/m2 every 3 weeks	Drug: Cyclophosphamide CTX Other Names: CTX Drug: Trastuzumab H Other Names: Herceptin Drug: Docetaxel DOC Other Names: Taxotere Drug: Epirubicin EPI Other Names: EPI

Arm

Intervention/Treatment

Experimental: ACH-TH

Doxorubicin liposome（PLD）35 mg/m2 Cyclophosphamide（CTX）600 mg/m2 Trastuzumab：first cycle 8mg/kg，then 6mg/kg Docetaxel（DOC）75 mg/m2 every 3 weeks

Drug: Doxorubicin liposome

PLD

Other Names:

PLD

Drug: Cyclophosphamide

CTX

Other Names:

CTX

Drug: Trastuzumab

Other Names:

Herceptin

Drug: Docetaxel

DOC

Other Names:

Taxotere

Active Comparator: EC-TH

Epirubicin（EPI）90 mg/m2 Cyclophosphamide（CTX）600 mg/m2 Trastuzumab：first cycle 8mg/kg，then 6mg/kg Docetaxel（DOC）75 mg/m2 every 3 weeks

Drug: Cyclophosphamide

CTX

Other Names:

CTX

Drug: Trastuzumab

Other Names:

Herceptin

Drug: Docetaxel

DOC

Other Names:

Taxotere

Drug: Epirubicin

EPI

Other Names:

EPI

Outcome Measures

Primary Outcome Measures

Pathological Complete Response rate (pCR) [At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug).]
Pathological complete response (pCR) in the breast tissue and the lymph node tissue will be assessed upon completion of pre-operative systemic therapy and definitive surgery.

Secondary Outcome Measures

Objective response rate (ORR) [Approximately 20-24 weeks from first dose of study drug]
CRR is defined as the proportion of subjects with complete or partial radiographic response of the primary tumor as determined by the central imaging vendor.
Event Free Survival (EFS) [Up to 5 years from the date of definitive surgery]
EFS will be defined as the time from random assignment to documentation of the first of the following events: discontinuation of study therapy due to protocol-defined progression prior to surgery; local, regional, or distant recurrence of breast cancer following curative surgery; a new breast cancer; another new onset malignancy; or death as a result of any cause.
Overall Survival (OS) [Up to 5 years from the date of definitive surgery.]
OS will be defined as the number of days from the day the subject is randomized to the date of the subject's death.
Incidence of chemotherapy-induced cardiotoxicity [Approximately 20-24 weeks from first dose of study drug]
Incidence of chemotherapy-induced cardiotoxicity, according to NCI-CTCAE 4.03 version.
Change From Baseline Between Treatment Comparison in Euro Quality of Life (EQ-5D) Index [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)]
The EuroQol EQ-5D is a 6-item instrument designed to assess health status in terms of a single index value or utility score. It contains 5 descriptors of current health state (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with each dimension having 3 levels of function (1=no problem, 2=some problem, and 3=extreme problem). The scores on the 5 descriptors are summarized to create a single summary score. An overall utility score is calculated based on these domains, with a range score from 0 (worse health scenario) to a maximum of 1.0 (best health scenario).
Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy -Breast (FACT-B) [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)]
FACT is a modular approach to assess participant health-related quality of life using a 'core' set of questions (FACT-G) as well as a cancer site-specific module. The FACT-G is a 27-item compilation of general questions divided into 4 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. The FACT-B consisted of the FACT-G (27-item) and a breast-specific module: a 10-item instrument designed to assess participant concerns relating to breast cancer. For all questions, participants were asked to respond to a five-level scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. FACT-B total score = Physical Well-Being + Social/Family Well-Being + Emotional Well-Being + Functional Well-Being + Breast Cancer Subscale. As each of the items ranges from 0-4, the range of possible scores is 0-144, with 0 being the worst possible score and 144 the best.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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