Efficacy and Safety of Neoadjuvant DC-T in Breast Cancer Patients (ESNDBCP)

The Efficacy and Safety of Neoadjuvant Pegylated Liposomal Doxorubicin Plus Cyclophosphamide Followed by Docetaxel in Breast Cancer Patients: A Multicentric, Open-label, Non-randomized Concurrent Control, Non-inferiority Trial

This is a multicentric, open-label,non-randomized concurrent control, 1:1 match,non-inferiority trial that assesses the efficacy and safety of neoadjuvant chemotherapy regimen DC-T and EC-T in breast cancer patients.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Pegylated liposomal doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Epirubicin

Detailed Description

OBJECTIVES: Determine the efficacy and safety of neoadjuvant chemotherapy regimen DC-T and EC-T in suitable breast cancer patients.

Participants are randomized to 1 of 2 treatment arms.

1. Arm I: Participants receive pegylated liposomal doxorubicin plus cyclophosphamide followed by docetaxel before surgery.
2. Arm II: Participants receive epirubicin plus cyclophosphamide followed by docetaxel before surgery.

Patients in arms I and II will undergo physical examination, MRI, estimating of side effects every 4 cycles referring to RECIST (Response Evaluation Criteria In Solid Tumor) guideline. To adjust for potential bias, patients in DC-T arm were matched 1:1 to patients in the EC-T arm based on Her-2 and ER status. After finishing 8 cycles of neoadjuvant chemotherapy, every patient will receive mastectomy or breast-conserving surgery and then assess the pCR rate of primary lesion and axillary lymph nodes. Adjuvant radiotherapy and endocrine therapy will be taken if necessary. Every patient will be followed-up for five years to monitor survival condition.

• Study Type: Interventional
• Enrollment (Anticipated): 384
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • Cancer Institute
      • Contact: Zhang Zhigang, Dr; Phone Number: 8657187315009; Email: zzg2011@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women aged : 18~70 years.
2. WHO (ECOG) performance status 0-2.
3. Patients who have read and understand the informed consent form and have given written informed consent.
4. Diagnosed as invasive breast cancer by core biopsy
5. Diagnosed pre-surgically as (cTNM Staging)Stage II-III and suit for neoadjuvant chemotherapy.
6. Patients had previously not received chemotherapy，radiotherapy or biotherapy.

7. Normal organ function，meeting the requirement of laboratory testing below:

   • WBC≥4.0×109/L,
   • NEU≥1.5×109/L,
   • PLT≥100×109/L,
   • HB ≥10g/dL,
   • Scr≤1.5× ULN,
   • AST ≤2.5×ULN,
   • ALT ≤2.5×ULN,
   • TDIL≤1.5×ULN.
8. Patients with measurable lesion assessed by imaging using the RECIST (Response Evaluation Criteria In Solid Tumor) guideline，（long diameter of primary lesion ≥1cm or minor diameter of lymph node ≥1.5cm）；

Exclusion Criteria:

1. Pregnant or lactating women were excluded.
2. History of receiving organ transplantation（including Autologous bone marrow transplantation and peripheral hematopoietic stem-cell transplantation).
3. Dysfunction of peripheral nerve system caused by other diseases or history of either severe mental disorder or central nervous system disorders.
4. Uncontrolled infection or severe peptic ulcer need treatment.
5. Severe hepatic disease（such as hepatic cirrhosis),nephrosis,respiratory disease or uncontrolled diabetes.
6. Patients with malignancies (other than breast cancer) within the last 5 years, except for adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin.
7. Significant abnormal EKG or cardiac disease with drastic symptoms like congestive heart failure or severe coronary disease or uncontrolled arrhythmia or myocardial infarction within 12 months or NYHA level III-IV or LVEF<55% .
8. Be allergic to test drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DC Follow T; Participants receive pegylated liposomal doxorubicin plus cyclophosphamide followed by docetaxel before surgery.	Drug: Pegylated liposomal doxorubicin; a new kind of doxorubicin; Other Names: PLD; Drug: Cyclophosphamide; traditional chemotherapy drug; Other Names: C; Drug: Docetaxel; traditional chemotherapy drug used in breast cancer; Other Names: T
ACTIVE_COMPARATOR: EC Follow T; Participants receive epirubicin plus cyclophosphamide followed by docetaxel before surgery.	Drug: Cyclophosphamide; traditional chemotherapy drug; Other Names: C; Drug: Docetaxel; traditional chemotherapy drug used in breast cancer; Other Names: T; Drug: Epirubicin; traditional chemotherapy drug used in breast cancer; Other Names: E

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate	The pathological complete response rate of primary lesion and axillary lymph nodes	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects	Determine side effects of these drugs like cardiotoxicity ,hematological toxicity，gastrointestinal symptoms and so on.	5 years
Overall survival	Determine the overall survival at 5 years.	5 years

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Zhejiang Cancer Hospital; First People's Hospital of Hangzhou; Second Affiliated Hospital, School of Medicine, Zhejiang University; First Affiliated Hospital of Zhejiang University; Women's Hospital School Of Medicine Zhejiang University; Sir Run Run Shaw Hospital; Zhejiang Provincial People's Hospital; First Affiliated Hospital of Wenzhou Medical University; Ningbo No. 1 Hospital; Jinhua Central Hospital; Zhejiang Provincial Hospital of TCM; Hangzhou Hospital of Traditional Chinese Medicine
• Investigators: Study Chair: Huang Jian, Dr, Second Affiliated Hospital of Zhejiang University School of Medicine

Publications and helpful links

General Publications

• O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9. doi: 10.1093/annonc/mdh097.
• Vici P, Pizzuti L, Gamucci T, Sergi D, Conti F, Zampa G, Del Medico P, De Vita R, Pozzi M, Botti C, Di Filippo S, Tomao F, Sperduti I, Di Lauro L. Non-pegylated liposomal Doxorubicin-cyclophosphamide in sequential regimens with taxanes as neoadjuvant chemotherapy in breast cancer patients. J Cancer. 2014 Apr 25;5(6):398-405. doi: 10.7150/jca.9132. eCollection 2014.
• Gil-Gil MJ, Bellet M, Morales S, Ojeda B, Manso L, Mesia C, Garcia-Martinez E, Martinez-Janez N, Mele M, Llombart A, Pernas S, Villagrasa P, Blasco C, Baselga J. Pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as primary chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: results of the phase II CAPRICE study. Breast Cancer Res Treat. 2015 Jun;151(3):597-606. doi: 10.1007/s10549-015-3415-2. Epub 2015 May 16.
• Uriarte-Pinto M, Escolano-Pueyo A, Gimeno-Ballester V, Pascual-Martinez O, Abad-Sazatornil MR, Agustin-Ferrandez MJ. Trastuzumab, non-pegylated liposomal-encapsulated doxorubicin and paclitaxel in the neoadjuvant setting of HER-2 positive breast cancer. Int J Clin Pharm. 2016 Apr;38(2):446-53. doi: 10.1007/s11096-016-0278-5. Epub 2016 Mar 7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2016
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: April 18, 2017
• First Posted (ACTUAL): April 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 10, 2019
• Last Update Submitted That Met QC Criteria: April 9, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Breast cancer; Pegylated liposomal doxorubicin; Neoadjuvant Chemotherapy; PLD
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Epirubicin; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: ESNDBCP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED