A randomized, multicenter, phase II trial comparing neo-adjuvant therapy using pertuzumab and trastuzumab emtansine based on the dual HER2 blockade in patients with operable HER2-positive primary breast cancer(Neo-peaks study)
- Conditions
- Female patients with operative HER2 positive primary breast cancer
- Registration Number
- JPRN-UMIN000014649
- Lead Sponsor
- Japan Breast Cancer Research Group(JBCRG)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- o longer recruiting
- Sex
- Female
- Target Recruitment
- 200
First key inclusion criteria
1)Age between 20 and 70 years
2)Female patients with primary breast cancer which is diagnosed as invasive cancer by needle biopsy or tissue biopsy.
3)Resectable primary breast cancer (cT1c-cT3,cN0-cN1,cM0)with a tumor size <=7cm in diameter.
4)The invasive component of the primary tumor is confirmed as HER2 positive(IHC 3+ or FISH+)
5)ER and PgR statuses are confirmed by IHC
6)No previous therapy for breast cancer
7)Pt has been confirned as suitable indication for primary systemic therapy
8)Pt who are able to undergo imaging evaluation of their primary disease using the same modality of contrast-enhanced MRI or PET/CT before the treatment,during the treatment,and at the end of the treatment.
9)Pt with evaluable primary disease using mammary ultrasonography before the treatment,during the treatment,and at the end of the treatment.
10)Written informed concents
Secondary criteria
By the pathological central review, HER2-positive invasive ductal carcionma, estrogen receptor and the Ki67 level has been confirmed.
1)ECOG performance status(PS)0-1
2)Laboratory test results meet the following criteria
neutrophil count=>1,500/mm3
Platelet count=>100,000/mm3
Hemoglobin=>9.0g/dL
Serum creatinine<=1.5xULN
AST and ALT<=1.25xULN
total bilirubin<=ULM(direct bilirubin<=ULM in case of Gilbert syndrome)
ALP<=1.5xULN
INR or APTT<=1.5xULN
3)Baseline LVEF=>55% measured by echocardiography or MUGA scan.
4)No QTc prolongation by ECG
5)No interstitial pneumonia or pulmonary fibrosis diagnosed by chest CT scan
6)Pt with confirmed menopausal status.
7)Pt who are not pregnant or who are confirmed not to be pregnant by pregnancy test(excluding patients who had hysterectomy).
8)Fertile patients must agree to use one"highly effective"form of nonhormonal contraception or two "effective" forms of nonhormonal contraception while on study and for more than 7 months after end of study treatment.
9)Pt with a positive hepatitis B surface antigen HBs antigen-positive patients cannot be enrolled.
1) Bilateral breast cancer whether synchronous or metachronous.Patients with controllable LCIS are permitted.
2)Pt with axillary lymph node dissection before pre-operative chemotherapy.
3)Pt with incisional or excisional biopsies for primary disease or axillary lymph node.
4)Pt with multiple malignancies.
5)Participation in another clinical trial
6)Pt with peripheral neuropathy >=NCI CTCAE v4.03 Grade 2 are excluded.
7)Pt with known cardiopulmonary dysfunction within 6 months before the 2nd enrollment are excluded
-Symptomatic left ventricular systolic dysfunction, severe cardiac arrhythmia uncontrolled by appropriate treatments.
-High-risk uncontrolled arrhythmias
-Uncontrolled hypertension,angina pectoris, clinically significant valvular heart disease.
-Requires continuous oxygen inhalation therapy.
-History of symptomatic congestive heart failure according to NCI CTCAE v4.03 or NYHA classification.
8)Pt with a history of myocardial infarction within 12 months before the 2nd enrollment.
9)Pt with severe uncontrolled systemic disease
10)Pt who have undergone major surgical operations or significant trauma within 28 days before the 2nd enrollment,or who have planned a major surgical operation during this study.
11)Pt with severe infectious disease requiring intravenous administration of antibiotics, antiviral agents,or antifungal agents at enrollment.
12)Pt with dental caries and/or oral infections requiring treatment.
13)Pt with diagnosed of active liver disease caused by autoimmune disease or sclerosing cholangitis.
14)Pt with obvious HIV infections.
15)Pt who are breast feeding.
16)History of uncontrolled seizures,central nervous system disorders,and mental disorders. Pt with diseases that could interfere with the informed consent process and/or compliance with protocol-based procedures as judged by investigator.
17)Known hypersensitivity to any of the study drugs or additives,including murine proteins.
18)Pt considered unfit as judged by the investigator.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method pCR
- Secondary Outcome Measures
Name Time Method SpCR, SpCR and ypN0 rate<br>CpCR rate<br>QpCR, QpCR and ypN0 rate<br>Overall response rate (ORR)<br>Breast-conserving surgery rate, and the proportion of breast-conserving surgery rate in patients who planned for mastectomy.<br>The proportion of patients not requiring lymph node dissection.<br>Disease-free survival and Progression-free survival<br>Overall Survival<br>To evaluate the safety profiles of each arm as follows;<br>Adverse events<br>Incidence of cardiac dysfunction