Clinical trial NCT02132949
Conditions: Breast Cancer
Sponsor: Hoffmann-La Roche
Start date: 2014-07-14; Completion date: 2020-08-25
Enrollment: 401 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This multicenter, non-randomized, open-label, phase 2 study is designed to evaluate the safety and efficacy of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and anthracycline-based chemotherapy as neoadjuvant treatment in participants with HER2-positive locally advanced, inflammatory, or early-stage breast cancer. Each investigator will choose a treatment regimen (A or B) for all of their participants to follow. Treatment regimen A (for Cohort A) will include dose-dense doxorubicin and cyclophosphamide (ddAC), followed by paclitaxel, with pertuzumab and trastuzumab given from the start of paclitaxel. Treatment regimen B (for Cohort B) will include 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), followed by docetaxel, with pertuzumab and trastuzumab given from the start of docetaxel. Participants in both cohorts will subsequently undergo surgical treatment and then resume pertuzumab and trastuzumab treatment.

Detailed description:

Arms: arm 1: Participants received neoadjuvant treatment with dose-dense doxorubicin and cyclophosphamide (ddAC), with administration of doxorubicin 60 milligrams per square meter (mg/m\^2) intravenously (IV) once every 2 weeks (q2w) and cyclophosphamide 600mg/m\^2 IV q2w for 4 cycles, followed by paclitaxel 80mg/m\^2 IV once weekly (qw) for 12 weeks. Pertuzumab (840 milligrams \[mg\] IV loading dose then 420mg IV q3w) and trastuzumab (8 milligrams per kilogram \[mg/kg\] IV loading dose then 4mg/kg IV q3w) were administered along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received adjuvant treatment with pertuzumab and trastuzumab IV q3w (up to 13 cycles), for a total of 17 cycles of pertuzumab and trastuzumab therapy during the study. Radiotherapy and adjuvant hormonal therapy were also given as clinically indicated. Following treatment completion/discontinuation, participants were followed for safety and efficacy for up to 5 years. arm 2: Participants received neoadjuvant treatment with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), with administration of 5-fluorouracil 500mg/m\^2 intravenously (IV) q3w, epirubicin 100mg/m\^2 IV q3w, and cyclophosphamide 600mg/m\^2 IV q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m\^2 in Cycle 5, then 100mg/m\^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab (840 mg IV loading dose then 420mg IV q3w) and trastuzumab (8 mg/kg IV loading dose then 4mg/kg IV q3w) were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received adjuvant treatment with pertuzumab and trastuzumab IV q3w (up to 13 cycles), for a total of 17 cycles of pertuzumab and trastuzumab therapy during the study. Radiotherapy and adjuvant hormonal therapy were also given as clinically indicated. Following treatment completion/discontinuation, participants were followed for safety and efficacy for up to 5 years.
Interventions: intervention 1: 5-Fluorouracil intervention 2: Cyclophosphamide intervention 3: Docetaxel intervention 4: Doxorubicin intervention 5: Epirubicin intervention 6: Paclitaxel intervention 7: Pertuzumab intervention 8: Trastuzumab
Intervention descriptions: intervention 1: Participants will receive 5-fluorouracil 500 mg/m\^2 IV on Day 1 of each cycle q3w. intervention 2: Participants will receive cyclophosphamide 600 milligrams per square meter (mg/m\^2) intravenous (IV) given on Day 1 of each cycle q2w. intervention 3: Participants will receive docetaxel at a starting dose of 75 mg/m\^2 IV for the first cycle and the dose may be escalated to 100 mg/m\^2 for subsequent cycles q3w. intervention 4: Participants will receive doxorubicin 60 mg/m\^2 IV on Day 1 of each cycle q2w. intervention 5: Participants will receive epirubicin 100 mg/m\^2 IV on Day 1 of each cycle q3w. intervention 6: Participants will receive paclitaxel 80 mg/m\^2 IV given weekly. intervention 7: Participants will receive pertuzumab at a loading dose of 840 milligrams (mg) IV loading dose, then 420 mg IV q3w. intervention 8: Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) IV, then 6 mg/kg IV q3w.

Protocol documents: