Patients with operable primary triple-negative breast cancer without prior treatment
Conditions
Interventions
Group A-1 Patient "
with age <
65 years and HRD positive"
with BRCA mutation"
1)Combination therapy (paclitaxel + carboplatin) 4 cycles ,2)FEC or AC therapy (4 cycles) ,3) surgery Combination therapy Cycles 1-4: paclitaxel at mg/m2 once every week (day 1, day 8, day 15) +
1)Combination therapy (eribulin + carboplatin)(4 cycles) ,2) FEC or AC therapy (4 cycles) ,3) surgery Combination therapy Cycles 1-4: eribulin at 1.4 mg/m2 (administered once weekly for two conse
65 years and HRD negative"
with age >
=65 years(without BRCA mutation)"
1)Combination therapy (eribulin + cyclophosphamide)(6 cycles) ,2) surgery However, the antitumor effects are examined at Cycles 4 and 6 to determine whether to continue combination therapy or convert
Sponsors
Japan Breast Cancer Research Group)
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: First key inclusion criteria (1) Age at the time of informed consent and has signed an informed consent form is between 20 and 70years (2) Primary breast cancer which is diagnosed as invasive breast cancer by needle or Vacuum-assisted breast biopsy (exclude apocrine or medullary carcinoma). (3) Resectable primary breast cancer (cT1c-cT3, cN0-cN1, and cM0)with a tumor size<=70mm in diameter. (4) Triple-negative (ER<1%, PgR<1%, and HER2-negative) is confirmed in primary lesion, Ki67 labelling index of>=10%. (5) No previous therapy for breast cancer. (6) Pt is considered as suitable indication for primary systemic therapy. (7) Pt who evaluable primary disease using contrast-enhanced MRI or PET/CT (8) Pt with evaluable primary disease using mammary ultrasonography (9) Written informed consent Secondary inclusion criteria Pt who has been determined to be eligible for the primary registration and meet all of the following conditions: (1) ECOG performance status (PS) 0-1 (2) By the pathological central review, invasive breast cancer, triple-negative breast cancer (ER <1%, PgR <1%, HER2 negative), and Ki67 labelling index of >=10% have been confirmed. (3) HRD test result is confirmed when age <65 years at consent acquisition (not required if BRCA mutations are known). (4) Clinical examination values at screening meet the criteria, with normal organ functions maintained. (5) Pt with HRD negative and the creatinine clearance >=50 mL/min when age >=65 years at consent acquisition. (6) No clinically significant arrhythmia by ECG (QTc: <=480 msec). (7) No interstitial pneumonia or lung fibrosis diagnosed by chest CT or X-ray. (8) Non-pregnancy is confirmed using a pregnancy test. (9) Pt with possibility of pregnancy must agree to take contraception. (10) HBs antigen, HBc antibody, and HBs antibody tests are all negative. In cases negative for HBs antigen and positive for HBc antibody and/or HBs antibody, HBV-DNA levels have to been below the detection limit.
Exclusion criteria
Exclusion criteria: (1) Bilateral invasive breast cancer whether metachronous,concurrent or bilateral DCIS. Contralateral DCIS after mastectomy (Bt), skin-sparing mastectomy (SSM), nipple-sparing mastectomy (NSM), or equivalent are permitted. (2) Pt with multiple cancers other than breast cancer (3) Pt with axillary lymph node dissection before pre-operative chemotherapy (4) Pt with incisional or excisional biopsies for primary lesion or axillary lymph node (5) Participation in another clinical trial within 28 days after the second registration (6) Pt with peripheral neuropathy >= NCI CTCAE v.4.03 Grade 2 (7) Pt with cardiopulmonary dysfunctions within six months before the second registration (8) Pt with myocardial infarction within 12 months before the second registration (9) Pt with severe uncontrolled systemic diseases (10) Pt who undergone major surgery or serious trauma within 28 days before the second registration, or who will have a major surgery during this trial. (11) Pt with severe infectious disease requiring intravenous administration of antibiotics, antiviral agents, or anti-fungal agents at the second registration (12) Pt with dental caries and/or oral infections requiring treatment (13) Pt with diagnosed of active liver disease or sclerosing cholangitis caused by autoimmune liver disorders (14) Pt with HIV infection (15) Lactating Pt (16)Other diseases that are considered to affect consent acquisition or protocol compliance by an investigator or sub-investigator. (17) Pt with hypersensitive to the study drug or additives and with DPD deficiency (18) Pt with difficulty of the oral ingestion, dysfunction of the upper gastrointestinal tract and malabsorption syndrome ( only in case HRD negative or age>=65 years at consent acquisition) (19) Pt determined to be ineligible by an investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological complete response evaluated by the Central Decision Institution [CpCRypN0 (ypT0-TisypN0)] | — |
Secondary
| Measure | Time frame |
|---|---|
| - SpCR, SpCR and pN0 rate - CpCR rate - QpCR, QpCR and pN0 rate - Clinical response rate (response rate of eribulin-based, anthracycline treatments and overall response rete) - Breast-conserving surgery rate - The rate of patients with axillary lymph nodes negative at the time of surgery which have been diagnosed as node positive before NAC. - Disease-free Survival (DFS), Invasive Disease-free survival (IDFS), overall survival (OS) (DFS, IDFS, and OS will be examined in an observational study after the completion of the investigator initiated clinical trial) - Influence of an eribulin combination regimen on the effects of the second half of the regimen (anthracycline) - Influence (e.g., neutrophil counts) of blood toxicity on Days 8 and 15 in Cycle 1 of the eribulin combination regimen on the therapeutic effects of eribulin and the effects of the second half of the regimen (anthracycline) - Influence (e.g., neutrophil counts) of blood toxicity on Days 8 and 15 in Cycle 1 of the paclitaxel combination regimen on the therapeutic effects of paclitaxel and the effects of the second half of the regimen (anthracycline) - Safety in each treatment groups (adverse events, completion rates, and dose intensity) | — |
Countries
Japan
Contacts
Public ContactJun Fukase
Japan Breast Cancer Research Group (JBCRG) Head office
Outcome results
None listed