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

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

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

Study Overview

• Status: Unknown
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: lapatinib/herceptin

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 Type: Interventional
• Enrollment (Anticipated): 482
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Sun Qiang, M.D.; Phone Number: 008613001289600; Email: wangxuefei63@pumch.cn

Study Locations

• China
  • Beijing, China, 100730
    • Recruiting
    • PUMCH
    • Contact: Sun Qiang, M.D.; Phone Number: 0086-13001289600; Email: 1210548954@qq.com
    • Contact: Wang Xuefei

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: EC→PL(Epirubicin+Cyclophosphamide--Docetaxel+lapatinib); 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;	Drug: lapatinib/herceptin; Lapatinib produced by glaxosmithkline. Oral small molecule epidermal growth factor tyrosine kinase inhibitor. Mainly used for combined with capecitabine in the treatment of ErbB-2 over expression, including received prior anthracycline, paclitaxel and trastuzumab (Herceptin) in the treatment of advanced or metastatic breast cancer. Our clinical trial want to see its benefit in early breast cancer
EXPERIMENTAL: PEL(Paclitaxel+epirubicin+Lapatinib); 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;	Drug: lapatinib/herceptin; Lapatinib produced by glaxosmithkline. Oral small molecule epidermal growth factor tyrosine kinase inhibitor. Mainly used for combined with capecitabine in the treatment of ErbB-2 over expression, including received prior anthracycline, paclitaxel and trastuzumab (Herceptin) in the treatment of advanced or metastatic breast cancer. Our clinical trial want to see its benefit in early breast cancer
ACTIVE_COMPARATOR: EC→PH(Epirubicin+Cyclophosphamide--Docetaxel+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	Drug: lapatinib/herceptin; Lapatinib produced by glaxosmithkline. Oral small molecule epidermal growth factor tyrosine kinase inhibitor. Mainly used for combined with capecitabine in the treatment of ErbB-2 over expression, including received prior anthracycline, paclitaxel and trastuzumab (Herceptin) in the treatment of advanced or metastatic breast cancer. Our clinical trial want to see its benefit in early breast cancer
ACTIVE_COMPARATOR: EPH(Paclitaxel+epirubicin+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	Drug: lapatinib/herceptin; Lapatinib produced by glaxosmithkline. Oral small molecule epidermal growth factor tyrosine kinase inhibitor. Mainly used for combined with capecitabine in the treatment of ErbB-2 over expression, including received prior anthracycline, paclitaxel and trastuzumab (Herceptin) in the treatment of advanced or metastatic breast cancer. Our clinical trial want to see its benefit in early breast cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS	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).	3 years& 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	0S is defined as the time from randomization to death due to any cause	5 years & 10 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
biomarker	A retrospective study was performed to examine the correlation between the prognosis of the two adjuvant and biomarkers, including but not limited to Ki67, PI3K, C-MYC, IGF1R, P95HER2, P53 and other biomarkers	5 years

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Taizhou EOC Pharma Co., Ltd.
• Investigators: Study Chair: Sun Qiang, M.D., PUMCH

Publications and helpful links

General Publications

• Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Dieras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. doi: 10.1200/JCO.2015.62.1797. Epub 2015 Nov 23. Erratum In: J Clin Oncol. 2019 Feb 1;37(4):356.
• Goss PE, Smith IE, O'Shaughnessy J, Ejlertsen B, Kaufmann M, Boyle F, Buzdar AU, Fumoleau P, Gradishar W, Martin M, Moy B, Piccart-Gebhart M, Pritchard KI, Lindquist D, Chavarri-Guerra Y, Aktan G, Rappold E, Williams LS, Finkelstein DM; TEACH investigators. Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Jan;14(1):88-96. doi: 10.1016/S1470-2045(12)70508-9. Epub 2012 Dec 10. Erratum In: Lancet Oncol. 2013 Feb;14(2):e47.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2017
• Primary Completion (ANTICIPATED): May 1, 2018
• Study Completion (ANTICIPATED): March 1, 2021

Study Registration Dates

• First Submitted: March 19, 2017
• First Submitted That Met QC Criteria: March 19, 2017
• First Posted (ACTUAL): March 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2017
• Last Update Submitted That Met QC Criteria: July 26, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: breast cancer; lapatinib; herceptin; her-2 positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Trastuzumab; Lapatinib
• Other Study ID Numbers: lapatinib

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After obtaining the primary endpoint, we will share our IPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No