Neoadjuvant Phase II Trial in Patients With T1c Operable, HER2-positive Breast Cancer According to TOP2A Status (NeoTOP)
Breast Cancer
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring HER2-positive, non-metastatic, TOP2A
Eligibility Criteria
Inclusion Criteria:
- Women aged ≥ 18;
- Patient has histologically confirmed breast cancer, with a clinical tumour diameter of > 1 cm (cT1c, cT2-3 or T4a)-
- Any N status
- No clinically or radiologically detectable metastases (M0);
- HR negative (both ER and PR < 10% by IHC); for T1c status, otherwise HR negative or positive
- Her-2 positive (i.e. IHC score 3+ or FISH/SISH/CISH positive);
- Performance status ≤ 1 (according to WHO criteria);
- Patients not previously treated by surgery, radiotherapy, hormone therapy or chemotherapy;
- Hæmatology: Absolute neutrophil count (ANC) ≥1,500/mm³; Platelets ≥100,000/mm³; Total white blood cell count (WBC) ≥3.000/mm³; Hb> 9g/dl;
- Hepatic Function: Total bilirubin ≤1.5 time the upper normal limit (UNL); ASAT ≤ 1.5xUNL; ALAT ≤ 1.5xUNL; Alkaline phosphatase ≤ 2.5xUNL;
- Renal Function: Serum creatinine ≤1.5xUNL (and if Serum creatinine >1.5xUNL, Creatinine clearance ≥50 mL/min (MDRD formula);
- Metabolic Function: Magnesium ≥ lower limit of normal; Calcium ≥ lower limit of normal;
- Patient with not controlled heart disease and for whom anthracyclines are not contraindicated. Cardiac ejection fraction ≥50% measured by MUGA or ECHO done within 4 weeks before inclusion;
- Patient agreeing to use effective contraception during and for ≥ 7 months after completion of study treatment;
- Patient able to comply with the protocol;
- Patient must have signed a written informed consent form prior to any study specific procedures;
- Patient must be affiliated to a Social Health Insurance.
Exclusion Criteria:
- Bilateral or multifocal breast cancer;
- Non-measurable tumour;
- Any form of breast cancer other than those described in the inclusion criteria, particularly inflammatory and/or overlooked forms (T4b or T4d);
- HER2 negative status (i.e. IHC score 0 or 1+, or IHC score 2+ and FISH/SISH/CISH negative);
- RH positive (ER or PR ≥ 10% by IHC) ;
- Patient has a history of second cancer, with exception of in situ cervical cancer or basocellular skin cancer which is regarded as cured;
- Patient has already been treated for new breast cancer;
- Patients have already undergone surgery for their disease or have had primary axillary dissection;
- Prior docetaxel administration or anti-HER2 antibody therapy (e.g.: trastuzumab or pertuzumab);
Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to:
- Heart or kidney failure, medullary, respiratory or liver failure, dyspnea
- Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia, poorly controlled hypertension) ≤ 1 year before enrollment
- Uncontrolled diabetes
- Significant neurological or psychiatric abnormalities
- Symptomatic or progressive disorder of the central nervous system (CNS) or metastasis at the initial check-up.
- Peripheral neuropathy > grade 2
- Acute urinary infection, ongoing hemorrhagic cystitis;
- Patients with a known history of HIV seropositivity;
- Sensitivity to any of the study medications or any of the ingredients or excipients of these medications;
- Patients receiving of the concomitant medications with phenytoin;
- Patients who received any other investigational drugs within 30 days of initiation of treatment and/or during the study;
- Must not have had a major surgical procedure within 30 days of initiation of treatment;
- Pregnant women, women who are likely to become pregnant or are breast-feeding;
- Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
- Patients with history of non compliance to medical regimens or unwilling or unable to comply with the protocol;
- Individual deprived of liberty or placed under the authority of a tutor.
Sites / Locations
- Institut de Cancerologie de L'Ouest - Site Paul Papin
- Centre Hospitalier Regional Universitaire de Brest - Hôpital Morvan
- Centre Francois Baclesse
- Centre Jean Perrin
- Chu de Grenoble - Hopital Michallon
- Chu de Limoges - Hôpital Dupuytren
- Centre Leon Berard
- Institut Regional Du Cancer Montpellier Val D'Aurelle
- Institut de Cancerologie de L'Ouest - Site Rene Gauducheau
- Hopital D'Instructions Des Armees
- Centre Paul Strauss
- Institut de Cancerologie de Lorraine Alexis Vautrin
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
TOP2A amplified
TOP2A not amplified
If TOP2A amplified: FEC x 3 then THP x 3 3 cycles of FEC 100 administered IV q3w 5-Fluorouracil (5-FU) 500 mg/m² Epirubicin 100 mg/m² Cyclophosphamide 500 mg/m² Followed by 3 cycles of Trastuzumab-Pertuzumab-Docetaxel: Trastuzumab 8 mg/kg loading dose administered intravenously (IV) followed by 6 mg/kg IV q3w in subsequent cycles. Pertuzumab 840 mg loading dose administered IV followed by 420 mg IV q3w in subsequent cycles. DOCETAXEL 75 mg/m² IV escalating at 100 mg/m² IV as tolerated q3w
If TOP2A not amplified: TCHP x 6 TCHP administered IV q3w for 6 cycles Trastuzumab 8 mg/kg loading dose administered IV followed by 6 mg/kg IV q3w in subsequent cycles. Pertuzumab 840 mg loading dose administered IV followed by 420 mg IV q3w in subsequent cycles. DOCETAXEL 75 mg/m² IV q3w CARBOPLATIN AUC 6 IV q3w The Calvert formula will be used to calculate the dose of carboplatin: Dose (mg) = target AUC (mg/mL x min) x [GFR mL/min + 25] Dose (mg) = 6 x [GFR mL/min + 25] NOTE: the Calvert formula gives the dose in mg, not mg/m². GFR, glomerular filtration rate The maximum dose of CARBOPLATIN must not exceed 900 mg.