Lapatinib Plus Chemotherapy Versus Trastuzumab Plus Chemotherapy in HER2-positive Breast Cancer
Primary Purpose
Neoplasms, Breast
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Lapatinib
Trastuzumab
Paclitaxel
Epirubicin
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms, Breast
Eligibility Criteria
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
Sites / Locations
- Xijing HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Control
Experimental group
Arm Description
Outcomes
Primary Outcome Measures
pathological complete response (pCR)
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03273595
Brief Title
Lapatinib Plus Chemotherapy Versus Trastuzumab Plus Chemotherapy in HER2-positive Breast Cancer
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Unknown status
Study Start Date
July 2016 (undefined)
Primary Completion Date
July 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xijing Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Breast
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Placebo Comparator
Arm Title
Experimental group
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Lapatinib
Intervention Type
Biological
Intervention Name(s)
Trastuzumab
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Type
Drug
Intervention Name(s)
Epirubicin
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Primary Outcome Measure Information:
Title
pathological complete response (pCR)
Time Frame
at the end of week 12
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rui Ling, Doctor
Phone
+862984775271
Email
lingrui0105@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Juliang Zhang, Doctor
Phone
+862984775271
Email
zhangjl@fmmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rui Ling, Doctor
Organizational Affiliation
Xijing Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Xijing Hospital
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juliang Zhang, Doctor
Phone
+862984775271
Email
zhangjl@fmmu.edu.cn
First Name & Middle Initial & Last Name & Degree
Juliang Zhang, Doctor
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
Lapatinib Plus Chemotherapy Versus Trastuzumab Plus Chemotherapy in HER2-positive Breast Cancer
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