Marched Pair Study Conventional Doxorubicin(DOX) Versus Pegylated Liposomal Doxorubicin(PLD) Neoadjuvant Chemotherapy

December 28, 2017 updated by: Aiping shi, Jilin University

Marched Pair Study of the Standard Chemotherapy 4doxorubicin Plus Cyclophosphamide(AC) 60 + 4 Docetaxel Protocol Versus 4 PLD C35+4 Docetaxel in Neoadjuvant Chemotherapy of Breast Cancer

The regimen PLD plus cyclophosphamide 4 cycles followed by paclitaxel or docetaxel 4 cycles(noted in phase II CAPRICE) will be used as experimental group. The regimen will be compared to the standard treatment of doxorubicin plus cyclophosphamide(AC) 4 cycles followed by paclitaxel or docetaxel 4 cycles[noted in National Comprehensive Cancer Network (NCCN) guideline].

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Purpose :Anthracycline based chemotherapy regimen is the milestone on the treatment of breast cancer . A sequential protocol, using docetaxel or Paclitaxel after an anthracycline-based combination is primary treatment for high-risk breast cancer .Despite its efficient antitumor activity profile, the use of conventional anthracycline in clinical practice is limited due to it's the risk of cardiac toxicity. The meta analysis show that subclinical cardiotoxicity was 17.9% whereas the incidence of clinically overt cardiotoxicity was 6.3%. Overall cardiovascular events occurred in 10.6%(Lotrisone , Am J Cardiol. 2013).Many patients have healed from breast cancer while they are snatched lives because of heart issue from chemotherapy using anthracycline. There are a lot of clinical trials exploring the possibilities of chemotherapy regimen without anthracycline ,however the recent result has shown anthracycline is indispensible for the patients whose axillary nodes are involved or triple negative breast cancer (ASCO 2016 ).So our target is to find a kind of anthracycline which is of equal efficiency with conventional anthracycline while less cardiac toxicity. Pegylated Liposomal Doxorubicin(PLD) is a novel kind of anthracycline. It distributes into cardiac cells lowly and releases Doxorubicin (DOX) slower to avoid peak plasma concentration, so it is of significant less cardiotoxicity compared to free DOX. It also achieve non-inferior efficacy at 50mg/m2 to conventional anthracycline in Metastatic Breast Cancer (MBC).( M. E. R. O'Brien, ,Annals of Oncology,2004;).

PLD 35mg/m2 in combination with paclitaxel showed an overall response rate of 71% ,tolerating toxicity of the skin(3% hand-foot syndrome)and rare cardiac event( H. Gogas1, Annals of Oncology, 2002;Gil-Gil , Breast Cancer Res Treat. 2015)However, There are a crucial question is to know if 35mg/m2 PLD has equivalent efficacy with less cardiac toxicity compared with 60 mg/m2 DOX in adjuvant chemotherapy for all patients.

The regimen PLD plus cyclophosphamide 4 cycles followed by paclitaxel or docetaxel 4 cycles(noted in phase II CAPRICE)will be used as experimental group. The regimen will be compared to the standard treatment of doxorubicin plus cyclophosphamide (AC)4 cycles followed by paclitaxel or docetaxel 4 cycles(noted in NCCN guideline).

Condition Intervention Phase

Individualized Chemotherapy Drug: Pegylated Liposomal Doxorubicin(PLD) Drug: Doxorubicin(DOX)

Drug: Cyclophosphamide Drug: docetaxel or Paclitaxel Phase 2

Study Type: Interventional Study Design: Allocation: assignment based on patients desire Endpoint Classification: Safety/Efficacy Study Intervention Model: Marched pair Parallel Assignment Masking: Open Label Primary Purpose: Treatment

Study Type

Interventional

Enrollment (Anticipated)

160

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 Locations

  • China
    • Jilin
      • Changchun, Jilin, China, 130021
        • Recruiting
        • First Hospital of Jilin University
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Di Wu, Doctor
        • Sub-Investigator:
          • Hongyao Jia, Master
        • Sub-Investigator:
          • Xin Guan, Master
        • Principal Investigator:
          • Zhimin Fan, Doctor
        • Principal Investigator:
          • Haibo Wang, Doctor
        • Sub-Investigator:
          • Gang Nie, Doctor

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

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Patient with histological proof of invasive cancer, whose clinical tumor diameter is > 2 cm, or < 2 cm, but Axillary lymphnodes are involved .There is no metastatic Imaging findings.
  • Stage II,III tumor, non-metastatic, grade II - III
  • Performance Status = 0-1 World Health Organization (WHO).
  • Patient non pretreated for breast cancer.
  • Patient without cardiac pathology and without anthracyclines contra-indication (assessed by normal ejection fraction).
  • Normal haematological, renal and hepatic functions : platelets > 100. 109 /l, Hb > 10 g/dl, normal bilirubin serum , Aspartate transaminase(ASAT) and Alanine Aminotransferase(ALAT) < 2,5 Upper Limit of Normal (ULN), alkaline phosphatases < 2,5 ULN, creatinin < 140 µmol/l or creatinin clearance > 60 ml/min
  • Written informed consent dated and signed by the patient

Exclusion Criteria:

  • All other breast cancers than those described in inclusion criteria, in particular inflammatory and/or neglected (T4b or T4d) forms.
  • Patient presenting with intraduct cancer in situ.(DCIS)
  • Grade I well differentiated tumor.
  • Non measurable lesion, in the two diameters, whatever radiological methods used.
  • Patient already operated for breast cancer or having had primary axillar node dissection.
  • Patient presenting with cancer in other system.
  • Any psychological, familial, sociological or geographical condition that may potentially hamper compliance with the study protocol and follow up schedule, assessed with the patient prior to registration in the trial

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: conventional Doxorubicin plus C-T
AC-T regimen 8 cycles ,60mg/M2 conventional Doxorubicin will be used as active comparator. four cycles of Doxorubicin plus 600mg/m2 Cyclophosphamide every three weeks followed 4 cycles of 100mg/m2 Taxotere, every three weeks for one cycle.Dexrazoxane (DZR)will be used for protecting cardiac toxicity.Patients will undergo Modified Radical Mastectomy or Breast Conserved Surgery or Axillary Lymph Node Dissection(ALND) or Sentinel Lymph Node Biopsy（SLNB） after 8 cycles of chemotherapy
Drug: Cyclophosphamide
600mg/m2 IV drop during the first 4 cycles every three week
Other Names:
  • cytoxan
Drug: Taxotere
100mg/m2 IV drop during the last 4 cycles every three week
Other Names:
  • Docetaxel
Drug: Dexrazoxane (DZR)
DZR will be administrated for protecting Cardiac toxicity in the group of Active comparator.
Other Names:
  • DZR
Drug: Doxorubicin
60mg/m2 Doxorubicin IV drop during the first 4 cycles every three week
Other Names:
  • Pirarubicin Hydrochloride for injection
Procedure: Breast Conserved Surgery
Patients will undergo Breast Conserved Surgery if the tumor/breast ratio is proper and she demands to conserve the breast after 8 cycles of chemotherapy
Other Names:
  • segmental mastectomy and ALND
Procedure: Modified Radical Mastectomy
Patients will undergo Modified Radical Mastectomy if she does not keep her breast after 8 cycles of chemotherapy
Other Names:
  • Mastectomy and ALND
Procedure: Sentinel Lymph Node Biopsy（SLNB）
Patients will undergo Sentinel Lymph Node Biopsy（SLNB） if the evaluation of lymph node are negative after 8 cycles of chemotherapy
Other Names:
  • Sentinel Lymph Node(SLN)
Experimental: PLD plus C -T
Pegylated Liposomal Doxorubicin(PLD) plus Cyclophosphamide followed Taxotere 8 cycles.35mg/M2 PLD will be used as experimental medicine. four cycles of PLD plus 600mg/m2 Cyclophosphamide every three weeks followed 4 cycles of 100mg/m2 Taxotere , every three weeks for one cycle.Vitamin B will be used for protecting hand-foot syndrome(HFS).Patients will undergo Modified Radical Mastectomy or Breast Conserved Surgery or Axillary Lymph Node Dissection(ALND) or Sentinel Lymph Node Biopsy（SLNB） after 8 cycles of chemotherapy
Drug: Cyclophosphamide
600mg/m2 IV drop during the first 4 cycles every three week
Other Names:
  • cytoxan
Drug: Taxotere
100mg/m2 IV drop during the last 4 cycles every three week
Other Names:
  • Docetaxel
Procedure: Breast Conserved Surgery
Patients will undergo Breast Conserved Surgery if the tumor/breast ratio is proper and she demands to conserve the breast after 8 cycles of chemotherapy
Other Names:
  • segmental mastectomy and ALND
Procedure: Modified Radical Mastectomy
Patients will undergo Modified Radical Mastectomy if she does not keep her breast after 8 cycles of chemotherapy
Other Names:
  • Mastectomy and ALND
Procedure: Sentinel Lymph Node Biopsy（SLNB）
Patients will undergo Sentinel Lymph Node Biopsy（SLNB） if the evaluation of lymph node are negative after 8 cycles of chemotherapy
Other Names:
  • Sentinel Lymph Node(SLN)
Drug: Pegylated Liposomal Doxorubicin
35mg/m2 iv drop during the first 4 cycles every three week
Other Names:
  • liposome doxorubicin injection
Drug: vitamin B
Vitamin B will be administrated for protecting HFS in PLD group
Other Names:
  • Compound Vitamin B

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
improvement of pathological complete response（PCR)
Time Frame: at th 26th weeks of treatment since recruitment (after 8 cycles of neoadjuvant chemotherapy when the patient will undergo surgery)
Pathological evaluation after sugary
at th 26th weeks of treatment since recruitment (after 8 cycles of neoadjuvant chemotherapy when the patient will undergo surgery)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tolerance according to Common Terminology Criteria Adverse Events (CTCAE) Version 4.0
Time Frame: at 3rd ,6th,9th,12th, 15 ,18,21,24th weeks since recruitment (after each cycle of chemotherapy) ; half year ,1 year , one and half year ,two years since recruitment
Cardiogram Cardiac sonography, examination of Cardiac Marker if necessary and Questionaire Survey about Side Effect
at 3rd ,6th,9th,12th, 15 ,18,21,24th weeks since recruitment (after each cycle of chemotherapy) ; half year ,1 year , one and half year ,two years since recruitment
Clinical Response Rate
Time Frame: at 3rd ,6th,9th,12th, 15 ,18,21,24th weeks since recruitment （after each cycle of chemotherapy）
ultrasound of breast and Pathological reports
at 3rd ,6th,9th,12th, 15 ,18,21,24th weeks since recruitment （after each cycle of chemotherapy）

Collaborators and Investigators

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

Sponsor

Jilin University

Investigators

  • Principal Investigator: Aiping Shi, Doctor, The First Hospital of Jilin University

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

November 1, 2016

Primary Completion (Anticipated)

November 1, 2019

Study Completion (Anticipated)

November 1, 2020

Study Registration Dates

First Submitted

October 8, 2016

First Submitted That Met QC Criteria

October 31, 2016

First Posted (Estimate)

November 2, 2016

Study Record Updates

Last Update Posted (Actual)

December 29, 2017

Last Update Submitted That Met QC Criteria

December 28, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016yx238

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

Jan 1,2018 to Dec ,31,2020

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

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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