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A multicenter randomized phase II clinical trial with neo -adjuvant chemotherapy containing eribulin mesylate for triple negative primary breast cancer patients (Neo-Entrance study)

Basic Information

Recruitment status	Complete: follow-up continuing
Health condition(s) or Problem(s) studied	Patients with operable primary triple-negative breast cancer without prior treatment
Date of first enrollment	2017/03/09
Target sample size	200
Countries of recruitment	Japan
Study type	Interventional
Intervention(s)	Group A-1 Patient "with age <65 years and HRD positive" or "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) + carboplatin AUC6 (once every three weeks (day 1) FEC or AC therapy Cycles 5-8: FEC therapy (5-fluorouracil: 500 mg/m2, epirubicin: 100 mg/m2, cyclophosphamide: 500 mg/m2) once every three weeks, or AC therapy (doxorubicin: 60 mg/m2, cyclophosphamide: 600 mg/m2) once every three weeks (No change during the FEC and AC therapies) Group A-2 Patient "with age <65 years and HRD positive" or "with BRCA mutation" 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 consecutive weeks and washout in Week 3 (day 1, day 8)) + carboplatin AUC6 (once every three weeks, day 1) FEC or AC therapy Cycles 5-8: FEC therapy (5-fluorouracil: 500 mg/m2, epirubicin: 100 mg/m2, cyclophosphamide: 500 mg/m2) once every three weeks, or AC therapy (doxorubicin: 60 mg/m2, cyclophosphamide: 600 mg/m2) once every three weeks (No change during FEC and AC therapies) Group B-1 Patient "with age <65 years and HRD negative" or "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 to FEC or AC therapy or surgery. Combination therapy Eribulin at 1.4 mg/m2 (administered once weekly for two consecutive weeks and washout in Week 3 (day 1,day 8)) + cyclophosphamide at 600 mg/m2 (once every three weeks, day 1) FEC or AC therapy FEC therapy (5-fluorouracil: 500 mg/m2, epirubicin: 100 mg/m2, cyclophosphamide: 500 mg/m2) once every three weeks, or AC therapy (doxorubicin: 60 mg/m2, cyclophosphamide: 600 mg/m2) once every three weeks) (No change during the FEC and AC therapies) Group B-2 Patient "with age <65 years and HRD negative" or "with age >=65 years(without BRCA mutation)" 1)Combination therapy (eribulin + capecitabine) (6 cycles) ,2) surgery However, the antitumor effects are examined at Cycles 4 and 6 to determine whether to continue combination therapy or convert to FEC or AC therapy or surgery. Combination therapy Cycles 1-6: eribulin at 1.4 mg/m2 (administered once weekly for two consecutive weeks and washout in Week 3 (day 1,day 8)) + capecitabine at 2,000 mg/m2/day (continuously administered twice daily on Days 1-14 and washout on Days 15-21) FEC or AC therapy FEC therapy (5-fulorouracil: 500 mg/m2, epirubicin: 100 mg/m2, cyclophosphamide: 500 mg/m2) once every three weeks, or AC therapy (doxorubicin: 60 mg/m2, cyclophosphamide: 600 mg/m2) once every three weeks) (No change during the FEC and AC therapies)

Outcome(s)

Primary Outcome

Pathological complete response evaluated by the Central Decision Institution [CpCRypN0 (ypT0-TisypN0)]

Secondary Outcome

- 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)

Key inclusion & exclusion criteria

Age minimum	20years-old
Age maximum	70years-old
Gender	Female
Include criteria
Exclude 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.