A Randomized Controlled Trial of HER-2 Positive Breast Cancer Patients Treated With Lapatinib vs Herceptin

Phase 2

• Conditions: HER2-positive Breast Cancer
• Interventions: Drug: lapatinib/herceptin

• Registration Number: NCT03085368
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

This is a randomized controlled trial of HER-2 positive breast cancer patients treated with lapatinib and paclitaxel vs herceptin and paclitaxel with sequential and synchronous anthracycline

Detailed Description

This is a randomized controlled trial of HER-2 positive breast cancer patients treated with lapatinib and paclitaxel vs herceptin and paclitaxel with sequential and synchronous anthracycline. Safety and efficacy are the primary endpoint. The positive expression of HER2 was confirmed by postoperative pathology in patients with breast adenocarcinoma (IDC). Patients who had not received any chemotherapy and targeted anti HER2 therapy.

In this study, the non inferiority design method, according to the wishes of patients and signed informed consent, randomly into the group, a total of 482 patients were enrolled in the trial group: the control group =1:1. The subjects were followed up for a total of 1 years, until the disease progressed, and the toxicity was not tolerated.

We want to study 84 months. The follow-up period was 5 years (the first adjuvant treatment time to the last follow-up) or the researchers decided to end the study.

Study Timeline

• Study Start: 2017-03-01
• Study First Submitted: 2017-03-19
• Study First Submitted QC: 2017-03-19
• Study First Posted: 2017-03-21
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-26
• Last Update Posted: 2017-07-28
• Primary Completion: 2018-05-01
• Study Completion: 2021-03-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 482

Inclusion Criteria

1. the first diagnosis of invasive breast cancer, confirmed by histology or cytology, and surgical resection of the primary lesions before receiving any anti breast cancer treatment;
2. female patients, aged 18 years and less than 80 years of age;
3. surgical resection of the primary tumor pathological examination, showed HER2 positive (defined as immunohistochemistry [IHC] 3+ or fluorescence in situ hybridization (FISH) positive);
4. hormone receptor status is known, lymph node positive or sentinel lymph node negative but high risk factors
5. the eastern oncology cooperative group (ECOG) patients with physical status score was 0 -2;
6. baseline LVEF >50%
7. the relevant institutional review board (IRB) or independent ethics committee (IEC) written informed consent

Exclusion Criteria

1. the subjects in pregnancy or lactation;
2. pregnant women may be within the first 7 days before pregnancy test positive (urine or serum).
3. received chemotherapy, endocrine or anti HER2 anti-tumor therapy;
4. congestive heart failure, unstable angina, heart failure or myocardial infarction and other diseases;
5. other invasive tumors (including the second primary breast cancer), may affect the outcome of the evaluation and program compliance; but the treatment of patients with disease free survival at least more than 5 years can be selected;
6. with chronic liver disease in patients with liver dysfunction and / or with clinical manifestations: the serum total bilirubin > 2.5 * ULN; or INR = 1.5 but no bilirubin. serum ALT or AST> * 3 * ULN; alkaline phosphatase >2.5 * ULN; ALT or AST can be gradually increased, but with gradually increasing fatigue, nausea and vomiting, fever, right upper quadrant pain or tenderness
7. hematopoietic dysfunction, defined as follows: neutrophil count (ANC) <1.5 * 109/L; platelet <100 * 109/L; hemoglobin <9 g/dL;
8. other serious diseases, including: congestive heart failure (heart function NYHA grade II, III, IV) or occurred within 6 months of congestive heart failure, unstable angina, arrhythmia, myocardial infarction patients can't control or other severe cardiovascular disease; breathing at rest or need oxygen therapy; serious infection; uncontrolled diabetes;
9. there is a serious psychological or mental abnormalities, estimated that the participants to participate in this study is not strong;
10. known to study drug allergy;
11. the past 30 days participated in the study of other drug clinical trials.

1, failed to complete the clinical trial of at least 1 cycles according to the program, can not carry out safety and efficacy evaluation 2, a serious violation of this research program, not in accordance with the prescribed dose, method and course of medication.

Patients will receive lapatinib treatment, until a predetermined end end point, or development of unacceptable toxicity, or withdrawal of consent, or illness or death, to appear before the subject.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EC→PL(Epirubicin+Cyclophosphamide--Docetaxel+lapatinib)	lapatinib/herceptin	Epirubicin 80 mg/ IV day M2 Cyclophosphamide 600 mg/m2 day IV 21 days for a total of 1 cycles, with a total of 4 cycles sequential Docetaxel 100mg/m2 IV day 1 21 days for a total of 1 cycles, with a total of 4 cycles Lapatinib 1000mg/d Po (fasting) every 30 days for a cycle Note: lapatinib in the first injection of docetaxel drug taking, once a day, oral dose of 1000mg, a total of over 1 years;
PEL(Paclitaxel+epirubicin+Lapatinib)	lapatinib/herceptin	80mg/ M2 day 1 IV epirubicin Paclitaxel 150mg/m2 IV day 1 14 days for a total of 1 cycles (intensive chemotherapy), with a total of 6 cycles Also given Lapatinib 1000mg/d Po (fasting) every 30 days for a cycle Note: lapatinib in the first injection of paclitaxel drug taking, once a day, oral dose of 1000mg, a total of over 1 years;
EC→PH(Epirubicin+Cyclophosphamide--Docetaxel+herceptin)	lapatinib/herceptin	Table 80mg/ day 1 IV Cyclophosphamide 600 mg/m2 day IV 21 days for a total of 1 cycles, with a total of 4 cycles Docetaxel 100mg/m2 IV day 1 21 days for a total of 1 cycles, with a total of 4 cycles Trastuzumab 2mg/kg IV QW (first dose 4 mg/kg) Note: trastuzumab was administered at the beginning of the first injection of paclitaxel, with an injection dose of 2mg/kg, 1 times a week, for a total of up to 1 years; followed by trastuzumab 2mg/kg IV, once every 3 weeks for a total of one year
EPH(Paclitaxel+epirubicin+herceptin)	lapatinib/herceptin	80mg/ M2 day 1 IV epirubicin Paclitaxel 150mg/m2 IV day 1 14 days for a total of 1 cycles, with a total of 6 cycles Also given Trastuzumab 2mg/kg IV QW (first dose 4 mg/kg) Note: trastuzumab was administered at the beginning of the first injection of paclitaxel, with an injection dose of 2mg/kg, 1 times a week, for a total of up to 1 years; followed by trastuzumab 2mg/kg IV, once every 3 weeks for a total of one year

Primary Outcome Measures

Name	Time	Method
DFS	3 years& 5 years	Since the first randomized to disease recurrence or death occurred due to other reasons, the recurrence of the disease include local, regional, distant, ipsilateral or contralateral breast cancer (excluding breast lobular carcinoma in situ) and non malignant tumor secondary breast (except the skin basal cell carcinoma or squamous cell carcinoma, cervical cancer in situ cancer).

Secondary Outcome Measures

Name	Time	Method
OS	5 years & 10 years	0S is defined as the time from randomization to death due to any cause

Trial Locations

Locations (1)

PUMCH; 🇨🇳 Beijing, China