Pegylated Liposomal Doxorubicin Plus Albumin-Bound Paclitaxel and Trastuzumab in HER-2 Positive Breast Cancer

A Single-center, Prospective, Single Arm Study of Neoadjuvant Treatment With Pegylated Liposomal Doxorubicin（PLD）Plus Albumin-Bound Paclitaxel and Trastuzumab in HER-2 Positive Breast Cancer

The purpose of this study is to evaluate the efficacy and safety of pegylated liposomal doxorubicin（PLD）plus Albumin-Bound Paclitaxel and trastuzumab as neoadjuvant therapy in HER-2 positive breast cancer.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Pegylated Liposomal Doxorubicin; Drug: Albumin-bound paclitaxel; Drug: Trastuzumab

Detailed Description

This is a single-center, prospective, single arm phase II study. Eligible patients will receive neoadjuvant therapy with pegylated liposome doxorubicin (PLD)/albumin-bound paclitaxel/trastuzumab regimentation.

This study consists of two phases, the first phase aims to determine the maximum tolerated dose (MTD) of PLD, and the second phase will explore the efficacy and safety of the regimen.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Fei Ma
      • Contact: Fei Ma, MD; Phone Number: +86-10-87787652; Email: mafei@126.com

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. Ability to understand and voluntarily receive the research procedures according to protocol,willingness to sign the written informed consent document;
2. Female patients aged from 18 to 70 years old;
3. Histologically confirmed as invasive breast cancer. occult breast cancer, inflammatory breast cancer and eczematoid carcinoma are ineligible;
4. Clinical stageⅡ-Ⅲ;
5. HER-2 Positive（defined by: IHC 3+ or ISH positive）;
6. Without previous treatment for this breast cancer;
7. Patients must have at least one measurable disease according to RECIST 1.1;
8. ECOG (Eastern Cooperative Oncology Group) performance score of 0-1 points;
9. LVEF≥55%;
10. Normal ECG;
11. Bone marrow function:absolute neutrophil count (ANC)≥2.0×109/L，platelets≥100×109/L，hemoglobin ≥90g/L。
12. Hepatic function：alanine aminotransferase(ALT) and aspartate aminotransferase(AST) ≤1.5×ULN，serum total bilirubin≤ ULN;
13. Renal function：serum creatinine≤1.5×ULN； Coagulation function：the international standardized ratio (INR) ≤1.5×ULN, prothrombin time (PT) or the activated partial thrombin time (APTT) ≤1.5×ULN.

Exclusion Criteria:

1. New York Heart Association (NYHA) class ≥Ⅱ heart failure.
2. Known or suspected hypersusceptibility to any agents used in the treatment protocol.
3. Need to Concurrent treatment with any other anti-cancer therapy considered by the investigator.
4. participating in other clinical trials within 4 weeks before this study.
5. Serious heart disease, including but not limited to:

1) Significant ventricular arrhythmia or high degree atrioventricular block (Mobitz II or third degree atrioventricular block); 2) unstable angina; 3) clinically significant heart valve disease; 4) Electrocardiogram shows transmural myocardial infarction; 5) Uncontrolled hypertension. 6. Uncontrolled diabetes. 7. Severe or uncontrolled infection. 8. Hepatitis b surface antigen positive, or hepatitis c virus antibody positive, or human immunodeficiency virus (HIV) antibody positive.

9. Active malignancy, other than adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin，within the past 5 years.

9）Women who are pregnant , breastfeeding ,or refuse to use adequate contraception prior to study entry and for the duration of study participation.

10）Other conditions considered to be inappropriate to be enrolled by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PLD/albumin-bound paclitaxel/Trastuzumab; First phase PLD: Level 1：30mg/m2； Level 2：35mg/m2； Level 3：40mg/m2； IV, d1, q21d×6. albumin-bound paclitaxel: 220mg/m2 IV for the first infusion，Subsequent infusions 260mg/m2,if no serious adverse reactions occur. d1, q21d×6. Trastuzumab：8mg/kg IV for the first infusion , Subsequent infusions 6mg/kg. d1, q21d×6. Second phase PLD: maximum tolerated dose (MTD). IV, d1, q21d×6. albumin-bound paclitaxel: 220mg/m2 IV for the first infusion，Subsequent infusions 260mg/m2,if no serious adverse reactions occur. d1, q21d×6. Trastuzumab：8mg/kg IV for the first infusion ,Subsequent infusions 6mg/kg. d1, q21d×6.

Drug: Pegylated Liposomal Doxorubicin; First phase PLD: 30mg/m2；35mg/m2；40mg/m2；IV, d1, q21d×6. Second phase PLD：MTD. IV, d1, q21d×6.; Drug: Albumin-bound paclitaxel; 220mg/m2 IV for the first infusion，Subsequent infusions 260mg/m2,if no serious adverse reactions occur. d1, q21d×6.; Drug: Trastuzumab; 8mg/kg IV for the first infusion. Subsequent infusions 6mg/kg. d1, q21d×6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response(pCR) rate	Percentage of patients who do not exhibit residual invasive breast cancer in breast and lymph nodes at time of surgery	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Breast conserving surgery	Percentage of patients undergoing breast-conserving surgery after neoadjuvant therapy	5 months
Rate of surgery	Percentage of patients undergoing mastectomy and breast-conserving surgery after neoadjuvant therapy	5 months
adverse events	Incidence and Severity of adverse events ,according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0	5 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College
• Collaborators: CSPC Ouyi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: June 19, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 20, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Paclitaxel; Trastuzumab; Albumin-Bound Paclitaxel; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: CSPC-DMS-BC-17

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No