BOOG study center
Dr. G.S. Sonke
M. van Ramshorst (NKI, m.v.ramshorst@nki.nl) A.E. van Leeuwen-Stok (BOOG Study Center)
Randomization: NKI Data Center, Trial Office P.O. Box 90203 1006 BE Amsterdam Phone +31 20 512 2668 Fax +31 20 512 2679 E-mail trial@nki.nl Central contact Data Centre: I. Mandjes NKI Data Center Phone +31 20 512 2667 Fax +31 20 512 2679 E-mail i.mandjes@nki.nl
NKI Data Center, Emmie van Schaffelaar Phone +31 20 512 2655 Fax +31 20 512 2679 E-mail e.v.schaffelaar@nki.nl
Contracts & finances: BOOG Study Center (info@boogstudycenter.nl)
R: chemotherapy randomization for all eligblepatients FEC-T cycle of 3 weeks F = 5-fluorouracil 500 mg/m2; E = epirubicin 90 mg/m2; C = cyclophosphamide 500 mg/m2; T = trastuzumab 6 mg/kg (loading dose 8 mg/kg) PTC cycle of 3 weeks, day 1 PTC, day 8 only P P = paclitaxel 80 mg/m2; T = trastuzumab 6 mg/kg (loading dose 8 mg/kg); C = carboplatin AUC = 6 mg.min/ml Pertuzumab (Ptz) cycle of 3 weeks, 420 mg (loading dose 840 mg) * Local treatment of breast (and axilla if necessary) with evaluation of pathologic response Post-surgery all patients will receive trastuzumab as per local standard of care, as well as endocrine treatment (only for ER positive patients), additional surgery, and/or radiotherapy as required. Post-surgery, different forms of trastuzumab, including subcutaneous trastuzumab are allowed.
Primary objectives 1. To compare the efficacy of six cycles neoadjuvant PTC plus pertuzumab preceded by either three cycles of FEC-T plus pertuzumab or three cycles of PTC plus pertuzumab in HER2 positive breast cancer Secondary objectives 1. To describe the safety of the various regimens 2. To identify prognostic and predictive biomarkers for pCR after neoadjuvant treatment
Primary endpoint
The primary endpoint is pathologic complete response (pCR) rate at surgery.
Secondary endpoints
– Recurrence-free, distant metastasis-free, breast cancer specific, and overall survival (time from randomization to event)
– Percentage of conservative surgeries carried out
– Percentage of patients with grade >2 toxicity (CTCAE v4.03)
1. Histologically confirmed infiltrating breast cancer 2.Stage II or stage III disease. Nodal status must be examined by ultrasound, fine needle aspiration,sentinel node biopsy, or FDG-PET scan. 3. Overexpression and/or amplification of HER2 in an invasive component of the core biopsy,according to one of the following definitions: >30% of invasive tumor cells showing strong complete circumferential membrane staining (score 3+) HER2 gene amplification defined as >6 HER2 gene copies per nucleus by in situ hybridization. 4.Age ≥18 5.Eastern Cooperative Oncology Group performance status ≤1 6.No previous radiation therapy or chemotherapy 7. No other malignancy except carcinoma in situ, unless the other malignancy was treated ≥5 years ago with curative intent without the use of chemotherapy or radiation therapy. 8. Adequate bone marrow function (ANC >1.5 x 109/l, platelets >100 x 109/l) 9. Adequate hepatic function (ALAT, ASAT and bilirubin <2.5 times upper limit of normal) 10. Adequate renal function (creatinine clearance >50 ml/min) 11. LVEF ≥50% measured by echocardiography or MUGA 12. No current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection 13. No evidence of distant metastases. Evaluation of the presence of distant metastases may include chest X-ray, liver ultrasound, isotope bone-scan, CT-scan of chest and abdomen and/or FDG-PET scan, according to local procedures. 14. No evidence of bilateral infiltrating breast cancer. Evaluation of the presence of bilateral infiltrating breast cancer may include mammography, breast ultrasound and/or MRI breast. 15. No concurrent anti-cancer treatment or another investigational drug. 16. Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 17. Absence of any medical condition that would place the patient at unusual risk 18. Signed written informed consent
