Study of Neoadjuvant Myocet®, Paclitaxel, Pertuzumab, and Trastuzumab in HER2-positive Breast Cancer

Study Overview
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Brief Summary
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This is a prospective, multicenter, single-arm, phase II study to evaluate the safety of neoadjuvant liposomal doxorubicin plus paclitaxel, trastuzumab, and pertuzumab in patients with HER2-positive breast cancer

Official Title
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OptiHER-Heart: A Prospective, Multicenter, Single-arm, Phase II Study to Evaluate the Safety of Neoadjuvant Liposomal Doxorubicin (Myocet®) Plus Paclitaxel, Trastuzumab, and Pertuzumab in Patients With HER2-positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Liposomal Doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures Female patients Age 18-74 years ECOG Performance Status of 0 or 1 Histologically confirmed, untreated, invasive breast carcinoma stage II-IIIB Tumor size > 2 cm by clinical or radiological assessment HER2+ invasive BC according to ASCO/CAP guidelines Known hormone receptor status or the possibility of its assessment Adequate organ function defined as: Absolute Neutrophil Count (ANC) ≥ 1.5 x 10**9/L Hemoglobin (Hgb) ≥ 9 g/dL Platelets > 100 x 10**9/L Creatinine ≤ 1.6 mg/dL ALT and AST ≤ 2.5 x ULN Alkaline phosphatase ≤ 5 ULN Total bilirubin ≤ 1.5 mg/dL Baseline LVEF ≥ 55% measured by echocardiogram or MUGA scan Negative β-HCG pregnancy test (serum) for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after the menopause. All subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control from 2 weeks before administration of the first dose of investigational product until 28 days after the last dose of investigational product Absence of 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 Exclusion Criteria: Clinical or radiologic evidence of metastatic disease at the time of study entry Prior chemotherapy, radiotherapy, or surgery for BC, other than excision of a tumor in the contralateral breast, and provided that the patient did not previously receive adjuvant radiotherapy or chemotherapy Subjects with a concurrently active second malignancy, other than adequately treated non melanoma skin cancers, in situ melanoma or in situ cervical cancer. Subjects with other non-mammary malignancies must have been disease-free for at least 5 years Known or suspected hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances Presence of CHF or LVEF < 55% Clinically significant (i.e. active) cardiovascular disease, including cerebrovascular accident (< 6 months before enrollment), unstable angina pectoris, myocardial infarction ≤ 6 months before enrollment, uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg), or high-risk uncontrolled arrhythmias Uncontrolled diabetes mellitus, active peptic ulcer disease, or uncontrolled epilepsy Active uncontrolled infection at the time of enrolment History of significant co-morbidities that, in the judgment of the investigator, may interfere with the conduction of the study, the evaluation of response, or with informed consent Use of any investigational agent or participation in another therapeutic clinical trial concurrently or in the previous 30 days before the enrollment Patients who are pregnant or breast-feeding Women of child-bearing potential who are unable or unwilling to use acceptable contraceptive measures Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liposomal Doxorubicin<br>Six cycles of: Trastuzumab 4 mg/kg loading dose on Day 1 of the first cycle, then 2 mg/kg on Days 8 and 15 of the first cycle and on Days 1, 8, and 15 of the subsequent cycles, every 3 weeks Pertuzumab 840 mg loading dose on Day 1 of the first cycle, then 420 mg on Day 1, every 3 weeks Liposomal doxorubicin 50 mg/m2 on Day 1, every 3 weeks Paclitaxel 80 mg/m2 on Days 1, 8, and 15, every 3 weeks | Drug: Liposomal Doxorubicin<br>* Six cycles of: Trastuzumab 4 mg/kg loading dose on Day 1 of the first cycle, then 2 mg/kg on Days 8 and 15 of the first cycle and on Days 1, 8, and 15 of the subsequent cycles, every 3 weeks Pertuzumab 840 mg loading dose on Day 1 of the first cycle, then 420 mg on Day 1, every 3 weeks Liposomal doxorubicin 50 mg/m2 on Day 1, every 3 weeks Paclitaxel 80 mg/m2 on Days 1, 8, and 15, every 3 weeks<br>* Other names: Myocet® (liposome-encapsulated doxorubicin);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of symptomatic (type A) and asymptomatic (type B) cardiac events during the study treatment period |  | Following 12 months after first dose of the study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR in breast (pCRB) |  | At the time of definitive surgery, an expected average of 23 weeks | 
| pCR in breast and axilla (pCRBA) |  | At the time of definitive surgery, an expected average of 23 weeks | 
| Clinical objective response rate (cORR) in the breast and axilla by RECIST criteria version 1.1 |  | At the time of definitive surgery, an expected average of 23 weeks | 
| Residual Cancer Burden (RCB) at surgery following the procedures of the MD Anderson Cancer Center |  | At the time of definitive surgery, an expected average of 23 weeks | 
| Breast conservation rate at surgery |  | At the time of definitive surgery, an expected average of 23 weeks | 
| Evaluation of serum biomarkers predictive of cardiotoxicity |  | Following 12 months after first dose of the study treatment | 
| Percentage of patients with grade 3/4 neutropenia (assessed by CTCAE v.4) |  | Following 12 months after first dose of the study treatment | 
| Time of onset and time of recovery from symptomatic (type A) and asymptomatic (type B) cardiac events (assessed by CTCAE v.4) |  | Following 12 months after first dose of the study treatment | 
| Dose reductions due to treatment toxicity (assessed by CTCAE v.4) |  | Following 12 months after first dose of the study treatment | 
| Dose delays due to treatment toxicity (assessed by CTCAE v.4) |  | Following 12 months after first dose of the study treatment | 
| Number of patients with adverse events and serious adverse events (assessed by CTCAE v.4) |  | Following 12 months after first dose of the study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, HER2 positive, Neoadjuvant, Liposomal doxorubicin, Paclitaxel, Trastuzumab, Pertuzumab, Safety