## Protocol Section
### Identification Module
**NCT ID:** NCT05656079

**Acronym:** easy laugh

**Brief Title:** To Evaluate the Cardiac Safety of Pegylated Liposomal Doxorubicin Concurrently Plus Trastuzumab and Pertuzumab in the Adjuvant Setting for Early-stage HER-2-positive Breast Cancer: a Multicenter, Randomized Controlled Clinical Study

**Official Title:** To Evaluate the Cardiac Safety of Pegylated Liposomal Doxorubicin Concurrently Plus Trastuzumab and Pertuzumab in the Adjuvant Setting for Early-stage HER-2-positive Breast Cancer: a Multicenter, Randomized Controlled Clinical Study

#### Organization Study ID Info
**ID:** kazuma
#### Organization
**Class:** OTHER
**Full Name:** Shanghai Pudong Hospital
### Status Module
#### Completion Date
**Date:** 2025-09

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-12-19

**Type:** ACTUAL

**Last Update Submit Date:** 2022-12-11

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-09

**Type:** ESTIMATED

#### Start Date
**Date:** 2021-07-01

**Type:** ACTUAL

**Status Verified Date:** 2022-12

#### Study First Post Date
**Date:** 2022-12-19
**Type:** ACTUAL
**Study First Submit Date:** 2022-12-11
**Study First Submit QC Date:** 2022-12-11
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** CSPC Ouyi Pharmaceutical Co., Ltd.

#### Lead Sponsor

**Class:** OTHER

**Name:** Shanghai Pudong Hospital

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** To evaluate the safety and efficacy of pegylated liposomal doxorubicin/cyclophosphamide/trastuzumab/pertuzumab followed by docetaxel/ trastuzumab/pertuzumab compared with epirubicin/cyclophosphamide followed by docetaxel/trastuzumab/pertuzumab in the adjuvant treatment of early breast cancer.

### Conditions Module

**Conditions:**

- Breast Cancer

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 204

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Pegylated liposomal doxorubicin 35 mg/m2, i.v. d1 +Cyclophosphamide 600 mg/m2 , i.v. d1 +Trastuzumab (8 mg/kg loading dose at first day only, then 6 mg/kg), i.v. d1+Pertuzumab (840 mg loading dose at first day only, then 420 mg), i.v. d1 ； q3w, for 4 cycles followed by Docetaxel 75mg/m2 , i.v. d1+ Pertuzumab 420 mg, i.v. d1+Trastuzumab 6 mg/kg, i.v. d1； q3w, for 4 cycles.

After the completion of adjuvant therapy, patients are required to receive a total of 1 year of treatment with trastuzumab combined with pertuzumab.

**Intervention Names:**

- Drug: Pegylated liposomal doxorubicin

- Drug: Cyclophosphamid

- Drug: Trastuzumab

- Drug: Pertuzumab

- Drug: Docetaxel

**Label:** pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Epirubicin 90 mg/m2 , i.v. d1 +Cyclophosphamide 600 mg/m2 , i.v. d1； q3w, for 4 cycles followed by Docetaxel 75mg/m2 , i.v. d1+Trastuzumab (8 mg/kg loading dose at first day only, then 6 mg/kg), i.v. d1+Pertuzumab (840 mg loading dose at first day only, then 420 mg), i.v. d1； q3w, for 4 cycles.

After the completion of adjuvant therapy, patients are required to receive a total of 1 year of treatment with trastuzumab combined with pertuzumab.

**Intervention Names:**

- Drug: Epirubicin

- Drug: Cyclophosphamid

- Drug: Trastuzumab

- Drug: Pertuzumab

- Drug: Docetaxel

**Label:** Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel

**Description:** Drug: Pegylated liposomal doxorubicin (35 mg/m2) will be administered by an intravenous infusion on day 1 of each21-day cycle.

**Name:** Pegylated liposomal doxorubicin

**Other Names:**

- duomeisu

- Doxorubicin Hydrochloride Liposome Injection

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab

**Description:** Drug: Epirubicin (90 mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle.

**Name:** Epirubicin

**Other Names:**

- biaoroubixing

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab

- pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel

**Description:** Drug: Cyclophosphamide (600 mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle.

**Name:** Cyclophosphamid

**Other Names:**

- huanlinxianan

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab

- pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel

**Description:** Drug: Trastuzumab (8 mg/kg loading dose at first day only, then 6 mg/kg) will be administered by an intravenous infusion on day 1 of each 21-day cycle.

**Name:** Trastuzumab

**Other Names:**

- qutuozhudankang

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab

- pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel

**Description:** Drug: Pertuzumab (840 mg loading dose at first day only, then 420 mg) will be administered by an intravenous infusion on day 1 of each 21-day cycle.

**Name:** Pertuzumab

**Other Names:**

- patuozhudankang

**Type:** DRUG

#### Intervention 6

**Arm Group Labels:**

- Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab

- pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel

**Description:** Drug: Docetaxel (75mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle.

**Name:** Docetaxel

**Other Names:**

- duoxitasai

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** 1-year incidence of cardiotoxicity

**Time Frame:** 1-year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. 18-70 years old, Female;
2. Subjects with histopathologically confirmed invasive breast cancer;
3. HER2-positive breast cancer (Immunohistochemistry score of 3+ or fluorescence in situ hybridization positivity);
4. No distant metastasis;
5. Lymph node positive or negative, primary tumour≥2cm;
6. Lymph node negative，primary tumour≤2cm and any of the following factors; 1) Histological grade 3; 2) ER negative (\<10%) and PR negative (\<20%); 3) Age\<35 years old; 4) Pathological hint: vascular invasion or intravascular cancer thrombus;
7. Surgery was completed and chemotherapy was started within 8 weeks after surgery;
8. Before and after chemotherapy LVEF≥55%;
9. ECOG performance status of 0-1;
10. Signed the informed consent.

Exclusion Criteria:

1. Subjects who are known to be allergic or intolerant to chemotherapy drugs or their excipients;
2. Previously suffered from invasive breast cancer, and other malignant tumors within 5 years (excluding carcinoma in situ of the cervix, carcinoma in situ of the rectum, carcinoma in situ of melanoma, basal cell carcinoma of the skin, and squamous cell carcinoma);
3. For breast cancer, have received any anti-tumor therapy before randomization (except surgical treatment before enrollment);
4. Hematopoietic function, renal function and liver function meet one of the following conditions: 1) Neutrophil count ≤1.5×109/L; 2) Platelet count ≤ 50×109/L; 3) Hemoglobin ≤ 8.0g/dL; 4) Creatinine clearance rate ≤30ml/min; 5) AST and ALT ≥ 2.5 times the upper limit of normal in subjects without liver metastases; 6) Bilirubin ≥ 2 times the upper limit of normal; 7) APTT/PT≥1.5 times the upper limit of normal;
5. Have a history of cardiovascular disease or associated with severe cardiovascular disease, lung disease;
6. Active hypertension: systolic blood pressure ≥ 180mmHg, diastolic blood pressure ≥ 90mmHg;
7. NYHA cardiac insufficiency grading ≥ Ⅲ grade;
8. Severe, uncontrollable systemic disease;
9. Subjects who are pregnant or breastfeeding, or subjects who cannot ensure effective contraceptive measures during the study treatment;
10. Subjects who participated in other clinical trials at the same time;
11. Subjects determined by the investigator to be inappropriate to participate in this study.

**Maximum Age:** 70 Years

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** liyongpingdt@sina.com

**Name:** Yongping Li

**Phone:** 021 68035102

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Email:** liyongpingdt@sina.com

- **Name:** Yongping Li

- **Role:** CONTACT

**Country:** China

**Facility:** Shanghai Pudong Hospital

**Status:** RECRUITING

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000001941

- Term: Breast Diseases

- ID: D000012871

- Term: Skin Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M5220

- Name: Breast Neoplasms

- Relevance: HIGH

- As Found: Breast Cancer

- ID: M5218

- Name: Breast Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001943

- Term: Breast Neoplasms

### Intervention Browse Module - Ancestors

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000018906

- Term: Antineoplastic Agents, Alkylating

- ID: D000000477

- Term: Alkylating Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000019653

- Term: Myeloablative Agonists

- ID: D000050257

- Term: Tubulin Modulators

- ID: D000050256

- Term: Antimitotic Agents

- ID: D000050258

- Term: Mitosis Modulators

- ID: D000000903

- Term: Antibiotics, Antineoplastic

- ID: D000059005

- Term: Topoisomerase II Inhibitors

- ID: D000059003

- Term: Topoisomerase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

### Intervention Browse Module - Browse Leaves

- ID: M6727

- Name: Cyclophosphamide

- Relevance: HIGH

- As Found: Cycle

- ID: M7492

- Name: Doxorubicin

- Relevance: HIGH

- As Found: Women

- ID: M227339

- Name: Liposomal doxorubicin

- Relevance: HIGH

- As Found: Sexual

- ID: M17954

- Name: Epirubicin

- Relevance: HIGH

- As Found: 12 hours

- ID: M1668

- Name: Docetaxel

- Relevance: HIGH

- As Found: Physical

- ID: M325

- Name: Trastuzumab

- Relevance: HIGH

- As Found: Medication

- ID: M289243

- Name: Pertuzumab

- Relevance: HIGH

- As Found: Safety Study

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20942

- Name: Antineoplastic Agents, Alkylating

- Relevance: LOW

- As Found: Unknown

- ID: M3820

- Name: Alkylating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M26197

- Name: Tubulin Modulators

- Relevance: LOW

- As Found: Unknown

- ID: M26196

- Name: Antimitotic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000003520

- Term: Cyclophosphamide

- ID: D000077143

- Term: Docetaxel

- ID: D000004317

- Term: Doxorubicin

- ID: C000506643

- Term: Liposomal doxorubicin

- ID: D000068878

- Term: Trastuzumab

- ID: D000015251

- Term: Epirubicin

- ID: C000485206

- Term: Pertuzumab

### Misc Info Module

- Version Holder: 2024-05-24
