Lapatinib Plus Chemotherapy Versus Trastuzumab Plus Chemotherapy in HER2-positive Breast Cancer

A Prospective, Open-label，Multicentre，Real-word Study of Lapatinib Plus Chemotherapy Versus Trastuzumab Plus Chemotherapy as Neoadjuvant Therapy for Women With HER2-positive and p95HER2-positive，PI3K Mutation，or PTEN Loss Breast Cancer

This is a prospective, open-label, real-word study evaluating the efficacy and safety of lapatinib in combination with chemotherapy versus trastuzumab in combination with chemotherapy in women with HER2-positive and p95HER2-positive ,or PI3K mutation, or PTEN loss breast cancer . Eligible subjects will have newly diagnosed breast cancer (Stage II-III) ; not have received systemic or local treatment . The primary endpoint was the rate of pathological complete response (pCR). The secondary objectives are to evaluate overall survival, overall response rate, clinical benefit response rate and the safety as well as tolerability of lapatinib plus chemotherapy and trastuzumab plus chemotherapy.

Patients will receive lapatinib 1000 mg daily or trastuzumab 4 mg/kg intravenous (IV) load followed by 2 mg/kg IV weekly for a total of 12 weeks. After surgery, patients planned total duration of the anti-HER2 therapy will be one year.

Study Overview

• Status: Unknown
• Conditions: Neoplasms, Breast
• Intervention / Treatment: Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Lapatinib; Biological: Trastuzumab

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rui Ling, Doctor; Phone Number: +862984775271; Email: lingrui0105@163.com

Study Locations

• China
  • Shanxi
    • Xi'an, Shanxi, China, 710032
      • Recruiting
      • Xijing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female gender;
• Age ≥18 years;
• Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
• Histologically confirmed invasive breast cancer:
• Primary tumour greater than 2 cm diameter, measured by clinical examination and mammography or echography,
• p95HER2 positive,or PI3K mutation,or PTEN loss
• Over expression and/or amplification of HER2 in the invasive component of the primary tumour [Wolff et al 2006] and confirmed by a certified laboratory prior to randomisation
• Known hormone receptor status.
• Haematopoietic status:
• Cardiovascular:
• Baseline left ventricular ejection fraction (LVEF) ³ 50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan,
• Negative serum pregnancy test, within 2-weeks (preferably 7 days) prior to randomization (For women of childbearing potential)
• Fertile patients must use effective contraception (barrier method - condoms, diaphragm - also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed)
• Signed informed consent form (ICF)
• Patient accepts to make available tumour samples for submission to central laboratory to conduct translational studies as part of this protocol

Exclusion Criteria:

• Received any prior treatment for primary invasive breast cancer;
• Previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated:
• Basal and squamous cell carcinoma of the skin;
• Carcinoma in situ of the cervix.
• Patients with a prior malignancy diagnosed more than 10 years prior to randomisation may enter the study. Patients must have been curatively treated with surgery alone. Radiation therapy or systemic therapy (chemotherapy or endocrine) are NOT permitted. Prior diagnoses of breast cancer or melanoma are excluded.
• Diagnosis of inflammatory breast cancer;
• Bilateral cancer;
• This criterion has been deleted from the protocol Version 1. Patients with multi-focal cancer are no longer excluded.
• Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnoea at rest, or chronic therapy with oxygen;
• Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety;
• Unresolved or unstable, serious adverse events from prior administration of another investigational drug;
• Active or uncontrolled infection;
• Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF;
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;
• Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies);
• Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial;
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab or lapatinib or their excipients;
• Pregnant or lactating women;
• Concomitant use of CYP3A4 inhibitors or inducers

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control	Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Biological: Trastuzumab
EXPERIMENTAL: Experimental group	Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Lapatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
pathological complete response (pCR)	at the end of week 12

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: Rui Ling, Doctor, Xijing Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (ANTICIPATED): July 1, 2019
• Study Completion (ANTICIPATED): December 1, 2019

Study Registration Dates

• First Submitted: February 22, 2017
• First Submitted That Met QC Criteria: September 4, 2017
• First Posted (ACTUAL): September 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2017
• Last Update Submitted That Met QC Criteria: September 4, 2017
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Trastuzumab; Epirubicin; Lapatinib
• Other Study ID Numbers: KY20162048-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No