A Randomised, Multicentre, Multinational Phase II Study to Evaluate Pertuzumab in Combination With Trastuzumab, Given Either Concomitantly or Sequentially With Standard Anthracycline-based Chemotherapy or Concomitantly With a Non-anthracycline-based Chemotherapy Regimen, as Neoadjuvant Therapy for Patients With Locally Advanced, Inflammatory or Early Stage HER2-positive Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pertuzumab
- Conditions
- Breast Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 225
- Primary Endpoint
- Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This 3 arm study will assess the tolerability, safety and efficacy of 3 neoadjuvant treatment regimens in participants with locally advanced, inflammatory or early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Before surgery, participants will be randomized to receive either A) 6 cycles of pertuzumab plus trastuzumab (Herceptin), with 5-fluorouracil/epirubicin/cyclophosphamide (FEC) for cycles 1-3 and docetaxel for cycles 4-6, or B) FEC for cycles 1-3 followed by pertuzumab plus trastuzumab with docetaxel for cycles 4-6, or C) 6 cycles of pertuzumab plus trastuzumab with docetaxel and carboplatin. Pertuzumab will be administered at a loading dose of 840 mg intravenously (iv), then 420 mg iv 3-weekly, trastuzumab at a loading dose of 8 mg/kg iv, then 6 mg/kg iv 3-weekly, docetaxel at 75 mg/m^2 iv, increased to 100 mg/m^2 iv 3-weekly, and FEC and carboplatin iv 3-weekly at standard doses. Following surgery participants will receive trastuzumab 6 mg/kg iv 3-weekly for a total of 1 year, as well as adequate chemo-, radio- and hormone therapy. Anticipated time on study treatment is 4-12 months, and target sample size is 200-300.
Investigators
Eligibility Criteria
Inclusion Criteria
- •female participants, age \>/=18 years
- •advanced, inflammatory or early stage unilateral invasive breast cancer
- •HER2-positive breast cancer
- •baseline left ventricular ejection fraction (LVEF) \>/=55%
Exclusion Criteria
- •metastatic disease (Stage IV) or bilateral breast cancer
- •previous anticancer therapy or radiotherapy for any malignancy
- •other malignancy, except for carcinoma in situ of the cervix, or basal cell carcinoma
- •clinically relevant cardiovascular disease
- •current chronic treatment with corticosteroids of \>10mg methylprednisolone or equivalent
Arms & Interventions
T+P Concomitant Anthracycline-based chemotherapy
5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
Intervention: Pertuzumab
T+P Concomitant Anthracycline-based chemotherapy
5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
Intervention: Trastuzumab
T+P Concomitant Anthracycline-based chemotherapy
5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
Intervention: FEC
T+P Concomitant Anthracycline-based chemotherapy
5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
Intervention: Docetaxel
T+P Sequential Anthracycline-based chemotherapy
FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.
Intervention: Pertuzumab
T+P Sequential Anthracycline-based chemotherapy
FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.
Intervention: Trastuzumab
T+P Sequential Anthracycline-based chemotherapy
FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.
Intervention: FEC
T+P Sequential Anthracycline-based chemotherapy
FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.
Intervention: Docetaxel
T+P Concomitant Non-Anthracycline chemotherapy
Trastuzumab, carboplatin, docetaxel (TCH) and pertuzumab (P) every three weeks, for six cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
Intervention: Pertuzumab
T+P Concomitant Non-Anthracycline chemotherapy
Trastuzumab, carboplatin, docetaxel (TCH) and pertuzumab (P) every three weeks, for six cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
Intervention: TCH
Outcomes
Primary Outcomes
Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator
Time Frame: From baseline up to approximately 3.5 years
Left ventricular systolic dysfunction (LVSD) as assessed by the Investigator, including Grade 3, 4 or 5 symptomatic LVSD with symptomatic cardiac events.
Safety: Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Decline During Pre-operative (Neoadjuvant) Period
Time Frame: From baseline up to approximately 18 weeks
Percentage of participants with LVEF measures decline of ≥ 10% from baseline and to a value of \<50% during the pre-operative (neoadjuvant) period.
Secondary Outcomes
- Efficacy: Percentage of Participants With Complete Pathological Response (pCR)(At surgery, after 18 weeks (6 cycles) of treatment)
- Efficacy: Clinical Response Rate(During each 3-week cycle of 6 total cycles: up to 18 weeks)
- Efficacy: Time to Clinical Response(Up to 18 weeks)
- Efficacy: Percentage of Participants Achieving Breast Conserving Surgery(At approximately 18 weeks)
- Efficacy: Percentage of Participants Without an Overall Survival (OS) Event(From baseline to end of study up to 5 years)
- Efficacy: Percentage of Participants Without a Disease-Free Survival (DFS) Event(From baseline to end of study up to 5 years)
- Efficacy: Percentage of Participants Without a Progression-Free Survival (PFS) Event(From baseline to end of study up to 5 years)
- Safety: Percentage of Participants With Cardiac Symptoms Associated With Symptomatic Left Ventricular Systolic Dysfunction (LVSD)(From Baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years))
- Safety: Percentage of Participants With Asymptomatic Left Ventricular Ejection Fraction (LVEF) Events(From baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years))
- Safety: Maximum Decrease in Left Ventricular Ejection Fraction (LVEF) Measures(From baseline up to approximately 3.5 years)