ACHP-THP vs EC-THP as Neoadjuvant Therapy for HER2-positive EBC
- Conditions
- Breast CancerNeoadjuvant Chemotherapy
- Interventions
- Registration Number
- NCT04172259
- Lead Sponsor
- Sun Yat-sen University
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 156
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ACHP-THP Paclitaxel-albumin 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 ACHP-THP Doxorubicin liposome 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 EC-THP Paclitaxel-albumin 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 ACHP-THP Docetaxel 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 ACHP-THP Cyclophosphamide 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 ACHP-THP Trastuzumab 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 ACHP-THP Pertuzumab 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 EC-THP Trastuzumab 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 EC-THP Docetaxel 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 EC-THP Epirubicin 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 EC-THP Cyclophosphamide 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 EC-THP Pertuzumab 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 EC-THP Paclitaxel 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
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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).
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.
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.
Trial Locations
- Locations (1)
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China