Efficacy and Safety of Dose-dense Chemotherapy (ddEC-ddP) for Neoadjuvant Chemotherapy of HER2-negative Breast Cancer

NCT04576143 | Recruiting Phase 2

• 1 other identifier: 2020-495
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief Summary

Recent clinical studies showed that breast cancer patients especially for those with lymph node metastasis may benefit from dose-dense chemotherapy, like adriamycin and cyclophosphamide (AC) q2w×4→ paclitaxel (P) q2w×4. However, the studies on dose-dense (dd) regimen chemotherapy is mostly based on postoperative adjuvant chemotherapy and the optimum of dose-dense chemotherapy has not been determined for Chinese population with HER2-negative breast cancer patients. In our study, a prospective, randomized, open-label, multi-center clinical study was conducted to compare the efficacy and safety of dose-dense chemotherapy regimen (dd epirubicin/cyclophosphamide (EC) followed by dd paclitaxel (P)) and conventional chemotherapy (epirubicin/cyclophosphamide (EC) followed by docetaxel (T)) as preoperative neoadjuvant chemotherapy in the treatment of HER2-negative breast cancer in Chinese population.

Conditions

HER2-negative Breast Cancer; Neoadjuvant Chemotherapy

Keywords

HER2-negative breast cancer; dose-dense chemotherapy; preoperative neoadjuvant chemotherapy; EC-T; ddEC-ddP

Outcome Measures

Primary Outcomes (1)

• pathological complete response (pCR)

  pCR is defined as the absence of noninvasive tumor residuals in breast and axillary lymph nodes (ypT0/is ypN0) after neoadjuvant therapy.

  Following the completion of 16 weeks or 24 weeks of neoadjuvant chemotherapy Treatment.

Secondary Outcomes (4)

• objective response rate (ORR)

  Following the completion of 16 weeks or 24 weeks of neoadjuvant chemotherapy Treatment.

• disease free survival (DFS)

  Time of Surgery up to 5 years

• breast-conserving rate (BCR)

  Following the completion of 16 weeks or 24 weeks of neoadjuvant chemotherapy Treatment.

• Number of participants with adverse events

  First Dose of chemotherapy up to 12 months.

Study Arms (2)

epirubicin/CTX × 4 - docetaxel × 4, every 3 weeks a cycle

ACTIVE COMPARATOR

Cycle 1-4: Epirubicin i.v. 90 mg/m2, Cyclophosphamide i.v. 600 mg/m2 (One cycle = 21 days); Cycle 5-8: Docetaxel i.v. 100mg/m2 (One cycle = 21 days) .

Drug: Epirubicin; Drug: Cyclophosphamid; Drug: Docetaxel

epirubicin/CTX × 4 - paclitaxel × 4, every 2 weeks a cycle

EXPERIMENTAL

Cycle 1-4: Epirubicin i.v. 90 mg/m2, Cyclophosphamide i.v. 600 mg/m2 (One cycle = 14 days); Cycle 5-8:Paclitaxel i.v. 175mg/m2 (One cycle = 14 days) .

Drug: Epirubicin; Drug: Cyclophosphamid; Drug: Paclitaxel

Interventions

Epirubicin DRUG

i.v. 90 mg/m2

Also known as: Epirubicin Hydrochloride

epirubicin/CTX × 4 - docetaxel × 4, every 3 weeks a cycle; epirubicin/CTX × 4 - paclitaxel × 4, every 2 weeks a cycle

Cyclophosphamid DRUG

i.v. 600 mg/m2

Also known as: CTX

epirubicin/CTX × 4 - docetaxel × 4, every 3 weeks a cycle; epirubicin/CTX × 4 - paclitaxel × 4, every 2 weeks a cycle

Docetaxel DRUG

i.v. 100 mg/m2

epirubicin/CTX × 4 - docetaxel × 4, every 3 weeks a cycle

Paclitaxel DRUG

i.v. 175 mg/m2

Also known as: PTX

epirubicin/CTX × 4 - paclitaxel × 4, every 2 weeks a cycle

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female aged 18-70 years old;
• Histological confirmed with unilateral invasive carcinoma (all pathological types are applicable), clinical stage IIA-IIIA;
• Definite reports on ER/PR/HER2 receptor showing all HER2 negative (HER2 is 0\~1+ or 2+ but determined negative via fluorescence in situ hybridization (FISH) or chemiluminescent in situ hybridization (CISH) detected (no amplification) is defined as HER2 negative);
• According to RECIST 1.1, there is at least one measurable objective focus, tumor size \> 2cm;
• Eastern Cooperative Oncology Group (ECOG) performance score is 0 or 1;
• Cardiac function: left ventricular ejection fraction (LVEF)≥55%;
• Normal bone marrow function: White blood cell count \> 4 × 10\^9/l, neutrophil count \> 1.5 × 10\^9/l, platelet count \> 100 × 10\^9/l and hemoglobin 9g/dl;
• Normal liver and renal function: aspartate aminotransferase (AST) and ALT ≤2.5 folds of the upper limit of normal values, total bilirubin ≤1.5 folds of the upper limit of normal values; Serum creatinine ≤1.5 folds of the upper limit of normal value.
• Informed consent form signed.

You may not qualify if:

• HER2 is positive;
• Metastasis at any location;
• Previous neoadjuvant therapy, including chemotherapy, radiotherapy and hormone therapy;
• Severe systemic disease and/or uncontrollable infection, unable to be enrolled in this study;
• Known allergic or intolerable to chemotherapeutic agents;
• Previously suffering from malignant tumors within 5 years (except for basal cell carcinoma and cervical carcinoma in situ), including contralateral breast cancer;
• Cardiovascular disease: LVEF \<50% (echocardiography) of New York Heart Association (NYHA) ≥ grade 2;
• Pregnant and breast-feeding women; Pregnancy test showed positive results before drug administration after enrolling in to the study; Women at childbearing age refuse to take contraception measures during the treatment and 8 weeks after completion of treatment;
• Already enrolled into other clinical trials;
• The researchers judged the patients who were not suitable for this study.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Women's Hospital School Of Medicine Zhejiang University: collaborator
• Changxing People's Hospital: collaborator
• Zhejiang Provincial People's Hospital: collaborator
• Hangzhou First People's Hospital, School of Medicine, Zhejiang Universiry: collaborator
• Huizhou Municipal Central Hospital: collaborator

Study Sites (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310000, China

RECRUITING

Related Publications (7)

• Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;(30):96-102. doi: 10.1093/oxfordjournals.jncimonographs.a003469.

  PMID: 11773300 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.

  PMID: 18258986 BACKGROUND

• Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project Protocol B-27. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003 Nov 15;21(22):4165-74. doi: 10.1200/JCO.2003.12.005. Epub 2003 Oct 14.

  PMID: 14559892 BACKGROUND

• Heys SD, Hutcheon AW, Sarkar TK, Ogston KN, Miller ID, Payne S, Smith I, Walker LG, Eremin O; Aberdeen Breast Group. Neoadjuvant docetaxel in breast cancer: 3-year survival results from the Aberdeen trial. Clin Breast Cancer. 2002 Oct;3 Suppl 2:S69-74. doi: 10.3816/cbc.2002.s.015.

  PMID: 12435290 BACKGROUND

• Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. doi: 10.1200/JCO.2003.09.081. Epub 2003 Feb 13.

  PMID: 12668651 BACKGROUND

• Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nistico C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella (GIM) investigators. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 x 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. doi: 10.1016/S0140-6736(14)62048-1. Epub 2015 Mar 2.

  PMID: 25740286 BACKGROUND

• Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Gounaris I, Abraham JE, Hughes-Davies L, McAdam K, Chan S, Ahmad R, Hickish T, Rea D, Caldas C, Bartlett JMS, Cameron DA, Provenzano E, Thomas J, Hayward RL; ARTemis Investigators Group. Disease-free and overall survival at 3.5 years for neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin and cyclophosphamide, for women with HER2 negative early breast cancer: ARTemis Trial. Ann Oncol. 2017 Aug 1;28(8):1817-1824. doi: 10.1093/annonc/mdx173.

  PMID: 28459938 BACKGROUND

MeSH Terms

Interventions

Epirubicin; Cyclophosphamide; Docetaxel; Paclitaxel

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Yiding Chen

  2nd Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yiding Chen

CONTACT

571-87784527; ydchen@zju.edu.cn

Huihui Chen

CONTACT

571-87784527; huihuicyj@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2020
• First Posted: October 6, 2020
• Study Start: September 20, 2020
• Primary Completion: June 20, 2023
• Study Completion (Estimated): September 20, 2027
• Last Updated: August 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)