Neoadjuvant Treatment Pegylated Liposomal Doxorubicin Plus Cyclophosphamide Sequential Docetaxel Plus Trastuzumab and Pertuzumab Versus Docetaxel Plus Carboplatin Combined With Trastuzumab and Pertuzumab in HER-2 Positive Breast Cancer

NCT05159193 | Recruiting Phase 3

• 1 other identifier: CSPC-DMS-BC-K07
• Study Type: interventional
• Target: 372
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open label, non-inferiority, randomized controlled clinical study. The aim of this study is to evaluate the efficacy and safety of a pegylated liposomal doxorubicin + cyclophosphamide followed by docetaxel plus trastuzumab and pertuzumab (PLD + C + HP followed by THP) regimen compared with a docetaxel + carboplatin plus trastuzumab and pertuzumab (TCbHP) regimen in the neoadjuvant treatment of HER-2-positive breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate

  The percentage of participants without residual invasive cancer (ypT0/Tis ypN0 in the current AJCC staging system) when the complete resected breast specimen and all sampled regional lymph nodes were evaluated with hematoxylin and eosin staining after completion of systemic neoadjuvant therapy.

  Within 2 to 5 weeks after completion of neoadjuvant therapy

Secondary Outcomes (7)

• Objective response rate (ORR) at the end of neoadjuvant chemotherapy

  After the last dose to before surgery or within 21 days

• 5-year disease-free survival (DFS) rate

  5 years

• Breast conservation rate at surgery

  Within 2 to 5 weeks after completion of neoadjuvant therapy

• Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V5.0, including overall and Grade 3/4 adverse events.

  5 years

• Percentage of Participants with dose reductions of chemotherapy due to Grade 3/4 adverse events as assessed by NCI-CTCAE V5.0

  1 year

Other Outcomes (2)

• Subgroup analysis of pathological complete response (pCR) rates based on clinically relevant baseline characteristics

  Within 2 to 5 weeks after completion of neoadjuvant therapy

• Biomarkers

  From before neoadjuvant therapy to surgery

Study Arms (2)

PLD + C + HP followed by THP

EXPERIMENTAL

pegylated liposomal doxorubicin (PLD) 30 mg/m\^2, i.v., d1 + cyclophosphamide (C) 600 mg/m\^2, i.v., d1 + trastuzumab (H) 8 mg/kg loading dose, 6 mg/kg maintenance doses, i.v., d1 + pertuzumab (P) 840 mg loading dose, 420 mg maintenance doses, i.v., d1 followed by docetaxel (T) 90\~100 mg/m\^2, i.v., d1 + trastuzumab (H) 6 mg/kg, i.v., d1 + pertuzumab (P) 420 mg, i.v., d1 q3w, for 4 cycles. After neoadjuvant therapy, patients are required to receive a total of 1 year of treatment with trastuzumab (6mg/kg) combined with pertuzumab (420mg), i.v., d1, q3w, regardless of surgery.

Drug: pegylated liposomal doxorubicin (PLD); Drug: cyclophosphamide (C); Drug: trastuzumab (H); Drug: pertuzumab (P); Drug: docetaxel (T)

TCbHP

ACTIVE COMPARATOR

docetaxel (T) 75 mg/m\^2, i.v., d1 + carboplatin (Cb) AUC 6, i.v., d1 + trastuzumab (H) 8 mg/kg loading dose, 6 mg/kg maintenance doses, i.v., d1 + pertuzumab (P) 840 mg loading dose, 420 mg maintenance doses, i.v., d1 q3w, for 6 cycles. After neoadjuvant therapy, patients are required to receive a total of 1 year of treatment with trastuzumab (6mg/kg) combined with pertuzumab (420mg), i.v., d1, q3w, regardless of surgery.

Drug: docetaxel (T); Drug: carboplatin (Cb); Drug: trastuzumab (H); Drug: pertuzumab (P)

Interventions

pegylated liposomal doxorubicin (PLD) DRUG

pegylated liposomal doxorubicin (PLD) 30 mg/m\^2, i.v., d1, q3w

Also known as: duomeisu, Doxorubicin Hydrochloride Liposome Injection

PLD + C + HP followed by THP

cyclophosphamide (C) DRUG

cyclophosphamide (C) 600 mg/m\^2, i.v., d1, q3w

Also known as: huanlinxianan

PLD + C + HP followed by THP

trastuzumab (H) DRUG

trastuzumab (H) 8 mg/kg loading dose, 6 mg/kg maintenance doses, i.v., d1, q3w

Also known as: qutuozhudankang

PLD + C + HP followed by THP

pertuzumab (P) DRUG

pertuzumab (P) 840 mg loading dose, 420 mg maintenance doses, i.v., d1, q3w

Also known as: patuozhudankang

PLD + C + HP followed by THP

docetaxel (T) DRUG

docetaxel (T) 90\~100 mg/m\^2, i.v., d1, q3w

Also known as: duoxitasai

PLD + C + HP followed by THP

carboplatin (Cb) DRUG

carboplatin (Cb) AUC 6, i.v., d1, q3w

Also known as: kabo

TCbHP

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 patients aged from 18 to 70 years old;
• Histologically confirmed as invasive breast cancer and without previous treatment.;
• HER-2 Positive (defined by IHC 3+ or ISH positive);
• Tumor \> 2cm;
• Biopsy pathology (FNAB or CNB) diagnosed regional lymph node metastasis within 28 days prior to randomization;
• Participants must have at least one measurable disease according to RECIST 1.1.
• Participants with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) are eligible provided all discrete lesions are sampled and centrally confirmed as HER2 positive.
• Operable breast cancer with cT2-cT4/cN1-cN3/cM0, according to the AJCC tumor staging manual (8th Edition).
• The HR(ER and PR) status of the primary tumor and the expression level of Ki-67 are clear.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• LVEF ≥ 55%;
• Brain natriuretic peptide (BNP) (or N-terminal pro brain natriuretic peptide (NT proBNP)) and cardiac troponin assays were within normal values.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and serum total bilirubin are all ≤2 ULN. Serum creatinine ≤ 1.5 ULN.
• Bone marrow function: white blood cell counts ≥ 3.0x10\^9/L, absolute neutrophil counts (ANC) ≥ 1.5x10\^9/L, platelets ≥ 100x10\^9/L, hemoglobin ≥ 90g/L;
• Participants had good compliance with the planned treatment and follow-up, understood the study procedures of this study, and signed informed consent form.

You may not qualify if:

• Breast cancer with distant metastasis;
• Participants with multiple lesions (in different quadrants) or bilateral breast cancer;
• Participants who have received prior anti-cancer therapy for breast cancer except those participants with a history of breast lobular carcinoma in situ (LCIS) that was surgically managed or ductal carcinoma in situ (DCIS) treated exclusively with mastectomy. In case of prior history of LCIS/DCIS, \>5 years must have passed from surgery until diagnosis of current breast cancer;
• In the past and present, participants with severe cardiac disease or discomfort , including but not limited: 1)High-risk uncontrolled arrhythmia, atrial tachycardia (heart rate \> 100/min in resting state), significant ventricular arrhythmia (ventricular arrhythmia) or higher atrioventricular block (second-degree type 2 \[Mobitz 2\] atrioventricular block or third-degree atrioventricular block); 2)Angina pectoris requiring anti-angina medication; 3)Clinically significant valvular heart disease; 4)ECG showing transmural myocardial infarction; 5)Uncontrolled hypertension (eg systolic blood pressure \> 180mm Hg or diastolic blood pressure \> 100mmHg); 6)Myocardial infarction; 7)Congestive heart failure;
• Participants have the following serious illnesses or medical conditions, including but not limited: 1)History of serious neurological or psychiatric disorders, including psychosis, dementia, or epilepsy, that prevent understanding and informed consent; 2)Active uncontrolled infection; 3)Active peptic ulcer, unstable diabetes;
• A history of other malignancies within the previous 5 years, except for adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin;
• Treatment with any investigational drug within 28 days prior to randomization;
• Participants who are known to be allergic to the active or other components of the study treatment or have contraindications for surgery;
• Participants who are pregnant, breastfeeding, or refuse to use adequate contraception prior to study entry and for the duration of study participation;
• Participants who were judged by the investigator to be unsuitable for this study.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• CSPC Ouyi Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Sunyat-sen Memorial Hospital

Guandong, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

liposomal doxorubicin; Cyclophosphamide; Trastuzumab; Protons; pertuzumab; Docetaxel; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Coordination Complexes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2021
• First Posted: December 16, 2021
• Study Start: December 20, 2021
• Primary Completion: October 30, 2024
• Study Completion (Estimated): January 31, 2028
• Last Updated: February 2, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)