ACHP-THP vs EC-THP as Neoadjuvant Therapy for HER2-positive EBC

October 12, 2023 updated by: Xia Wen, Sun Yat-sen University

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

156

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-Sen University Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ACHP-THP
Doxorubicin liposome（PLD）35 mg/m2 Cyclophosphamide（CTX）600 mg/m2 Trastuzumab：first cycle 8mg/kg，then 6mg/kg Pertuzumab：first cycle 840mg，then 420mg Docetaxel（DOC）75 mg/m2 every 3 weeks paclitaxel (PTX) 175 mg/m2 every 3 weeks or paclitaxel (PTX) 80 mg/m2 every week albumin-bound paclitaxel 260 mg/m2 or albumin-bound paclitaxel 100 mg/m2 every week
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
Drug: Pertuzumab
P
Drug: Paclitaxel-albumin
albumin-bound paclitaxel 260 mg/m2 or albumin-bound paclitaxel 100 mg/m2 every week
Active Comparator: EC-THP
Epirubicin（EPI）90 mg/m2 Cyclophosphamide（CTX）600 mg/m2 Trastuzumab：first cycle 8mg/kg，then 6mg/kg Pertuzumab：first cycle 840mg，then 420mg Docetaxel（DOC）75 mg/m2 every 3 weeks paclitaxel (PTX) 175 mg/m2 every 3 weeks or paclitaxel (PTX) 80 mg/m2 every week albumin-bound paclitaxel 260 mg/m2 or albumin-bound paclitaxel 100 mg/m2 every week
Drug: Cyclophosphamide
CTX
Other Names:
  • CTX
Drug: Trastuzumab
H
Other Names:
  • Herceptin
Drug: Docetaxel
DOC
Other Names:
  • Taxotere
Drug: Epirubicin
EPI
Other Names:
  • EPI
Drug: Pertuzumab
P
Drug: Paclitaxel-albumin
albumin-bound paclitaxel 260 mg/m2 or albumin-bound paclitaxel 100 mg/m2 every week
Drug: Paclitaxel
paclitaxel (PTX) 175 mg/m2 every 3 weeks or paclitaxel (PTX) 80 mg/m2 every week

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological Complete Response rate (pCR)
Time Frame: 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.
At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: 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.
Approximately 20-24 weeks from first dose of study drug
Event Free Survival (EFS)
Time Frame: 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.
Up to 5 years from the date of definitive surgery
Overall Survival (OS)
Time Frame: 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.
Up to 5 years from the date of definitive surgery.
Incidence of chemotherapy-induced cardiotoxicity
Time Frame: Approximately 20-24 weeks from first dose of study drug
Incidence of chemotherapy-induced cardiotoxicity, according to NCI-CTCAE 4.03 version.
Approximately 20-24 weeks from first dose of study drug
Change From Baseline Between Treatment Comparison in Euro Quality of Life (EQ-5D) Index
Time Frame: 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).
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)
Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy -Breast (FACT-B)
Time Frame: 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.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Collaborators

First Affiliated Hospital, Sun Yat-Sen University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Investigators

  • Principal Investigator: Wen Xia, MD, SunYat-Sen University Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 10, 2019

Primary Completion (Actual)

September 30, 2023

Study Completion (Estimated)

September 30, 2026

Study Registration Dates

First Submitted

December 18, 2018

First Submitted That Met QC Criteria

November 19, 2019

First Posted (Actual)

November 21, 2019

Study Record Updates

Last Update Posted (Actual)

October 16, 2023

Last Update Submitted That Met QC Criteria

October 12, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • METIS
  • SCBCG-023 (Other Identifier: South China Breast Cancer Group)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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