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

NCT ID: NCT05159193

Last Updated: 2024-02-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 372 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-20
• Study Completion Date: 2028-01-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PLD + C + HP followed by THP

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.

Group Type: EXPERIMENTAL

pegylated liposomal doxorubicin (PLD)

Intervention Type: DRUG

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

cyclophosphamide (C)

Intervention Type: DRUG

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

trastuzumab (H)

Intervention Type: DRUG

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

pertuzumab (P)

Intervention Type: DRUG

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

docetaxel (T)

Intervention Type: DRUG

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

TCbHP

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.

Group Type: ACTIVE_COMPARATOR

docetaxel (T)

Intervention Type: DRUG

docetaxel (T) 75 mg/m\^2, i.v., d1, q3w

carboplatin (Cb)

Intervention Type: DRUG

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

trastuzumab (H)

Intervention Type: DRUG

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

pertuzumab (P)

Intervention Type: DRUG

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

Interventions

pegylated liposomal doxorubicin (PLD)

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

Intervention Type: DRUG

cyclophosphamide (C)

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

Intervention Type: DRUG

trastuzumab (H)

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

Intervention Type: DRUG

pertuzumab (P)

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

Intervention Type: DRUG

docetaxel (T)

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

Intervention Type: DRUG

docetaxel (T)

docetaxel (T) 75 mg/m\^2, i.v., d1, q3w

Intervention Type: DRUG

carboplatin (Cb)

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

Intervention Type: DRUG

trastuzumab (H)

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

Intervention Type: DRUG

pertuzumab (P)

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

Intervention Type: DRUG

Other Intervention Names

duomeisu; Doxorubicin Hydrochloride Liposome Injection; huanlinxianan; qutuozhudankang; patuozhudankang; duoxitasai; duoxitasai; kabo; qutuozhudankang; patuozhudankang

Eligibility Criteria

Inclusion Criteria

1. Female patients aged from 18 to 70 years old;

2. Histologically confirmed as invasive breast cancer and without previous treatment.;

3. HER-2 Positive (defined by IHC 3+ or ISH positive);

4. Tumor > 2cm;

5. Biopsy pathology (FNAB or CNB) diagnosed regional lymph node metastasis within 28 days prior to randomization;

6. Participants must have at least one measurable disease according to RECIST 1.1.

7. 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.

8. Operable breast cancer with cT2-cT4/cN1-cN3/cM0, according to the AJCC tumor staging manual (8th Edition).

9. The HR(ER and PR) status of the primary tumor and the expression level of Ki-67 are clear.

10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

11. LVEF ≥ 55%;

12. Brain natriuretic peptide (BNP) (or N-terminal pro brain natriuretic peptide (NT proBNP)) and cardiac troponin assays were within normal values.

13. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and serum total bilirubin are all ≤2 ULN. Serum creatinine ≤ 1.5 ULN.

14. 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;

15. Participants had good compliance with the planned treatment and follow-up, understood the study procedures of this study, and signed informed consent form.

Exclusion Criteria

1. Breast cancer with distant metastasis;

2. Participants with multiple lesions (in different quadrants) or bilateral breast cancer;

3. 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;

4. 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;

5. 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;

6. 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;

7. Treatment with any investigational drug within 28 days prior to randomization;

8. Participants who are known to be allergic to the active or other components of the study treatment or have contraindications for surgery;

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

10. Participants who were judged by the investigator to be unsuitable for this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

CSPC Ouyi Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Sunyat-sen Memorial Hospital

Guandong, Guangdong, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Qiang Liu, PhD

Role: primary

victorlq@hotmail.com

86-020-34071157

Other Identifiers

CSPC-DMS-BC-K07

Identifier Type: -

Identifier Source: org_study_id