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| ID | Type | Description | Link |
|---|---|---|---|
| SCBCG-023 | Other Identifier | South China Breast Cancer Group |
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| Name | Class |
|---|---|
| First Affiliated Hospital, Sun Yat-Sen University | OTHER |
| Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ACHP-THP | Experimental | 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 | Active Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doxorubicin liposome | Drug | PLD |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Pathological Complete Response rate (pCR) | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wen Xia, MD | SunYat-sen University Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | 510060 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24399786 | Background | Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29. doi: 10.3322/caac.21208. Epub 2014 Jan 7. | |
| 6831397 | Background | Fisher B, Gunduz N, Saffer EA. Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases. Cancer Res. 1983 Apr;43(4):1488-92. |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D004317 | Doxorubicin |
| C041277 | 1-dodecylpyridoxal |
| D003520 | Cyclophosphamide |
| D000068878 | Trastuzumab |
| D000077143 | Docetaxel |
| D015251 | Epirubicin |
| C485206 | pertuzumab |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
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| Cyclophosphamide |
| Drug |
CTX |
|
|
| Trastuzumab | Drug | H |
|
|
| Docetaxel | Drug | DOC |
|
|
| Epirubicin | Drug | EPI |
|
|
| Pertuzumab | Drug | P |
|
| Paclitaxel | Drug | paclitaxel (PTX) 175 mg/m2 every 3 weeks or paclitaxel (PTX) 80 mg/m2 every week |
|
| Paclitaxel-albumin | Drug | albumin-bound paclitaxel 260 mg/m2 or albumin-bound paclitaxel 100 mg/m2 every week |
|
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) | 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 | 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 | 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) | 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) |
| 3798106 | Background | Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177-82. doi: 10.1126/science.3798106. |
| 526911 | Background | Goldie JH, Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep. 1979 Nov-Dec;63(11-12):1727-33. |
| 28700263 | Background | Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017 Aug 17;377(7):702. doi: 10.1056/NEJMx170011. Epub 2017 Jul 12. No abstract available. |
| 29146401 | Background | Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Chia SKL, Mansi J, Barrios CH, Gnant M, Tomasevic Z, Denduluri N, Separovic R, Gokmen E, Bashford A, Ruiz Borrego M, Kim SB, Jakobsen EH, Ciceniene A, Inoue K, Overkamp F, Heijns JB, Armstrong AC, Link JS, Joy AA, Bryce R, Wong A, Moran S, Yao B, Xu F, Auerbach A, Buyse M, Chan A; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1688-1700. doi: 10.1016/S1470-2045(17)30717-9. Epub 2017 Nov 13. |
| 25693012 | Background | Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortes J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. doi: 10.1056/NEJMoa1413513. |
| 28526536 | Background | Dieras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):732-742. doi: 10.1016/S1470-2045(17)30312-1. Epub 2017 May 16. |
| 28526538 | Background | Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic T, Hoersch S, Smitt M, Wildiers H. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol. 2017 Jun;18(6):743-754. doi: 10.1016/S1470-2045(17)30313-3. Epub 2017 May 16. |
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| 18258986 | Background | Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. doi: 10.1200/JCO.2007.15.0235. |
| D017437 |
| Skin and Connective Tissue Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D004224 | Diterpenes |
| D013729 | Terpenes |