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

Sponsor

SOLTI Breast Cancer Research Group (Other)

Overall Status

Completed

CT.gov ID

NCT01669239

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Liposomal Doxorubicin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

83 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2013

Actual Primary Completion Date :

Jan 1, 2016

Actual Study Completion Date :

Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Liposomal Doxorubicin 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 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 Other Names: Myocet® (liposome-encapsulated doxorubicin)

Arm

Intervention/Treatment

Experimental: Liposomal Doxorubicin

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

Other Names:

Myocet® (liposome-encapsulated doxorubicin)

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 74 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hospital Clínic de Barcelona	Barcelona	Spain
2	Hospital Universitario Vall d´Hebron	Barcelona	Spain
3	Complejo Hospitalario San Pedro de Alcántara	Cáceres	Spain
4	Hospital Universitari Arnau de Vilanova de Lleida	Lleida	Spain
5	Hospital Universitario 12 de Octubre	Madrid	Spain	28041
6	Centro Integral Oncológico Clara Campal	Madrid	Spain
7	Hospital Universitario Clínico San Carlos	Madrid	Spain
8	Hospital Universitario Puerta de Hierro de Majadahonda	Madrid	Spain
9	MD Anderson Cancer Center Madrid	Madrid	Spain
10	Hospital Universitario Virgen de la Arrixaca	Murcia	Spain
11	Hospital Son Llàtzer	Palma de Mallorca	Spain
12	Hospital Universitari Son Espases	Palma de Mallorca	Spain
13	Hospital Sant Joan de Reus	Reus	Spain
14	Hospital Sagrado Corazón USP	Sevilla	Spain
15	Hospital Universitario Virgen del Rocío	Sevilla	Spain
16	Hospital Virgen de la Macarena	Sevilla	Spain
17	Fundación Instituto Valenciano de Oncología	Valencia	Spain
18	Hospital Arnau de Vilanova de Valencia	Valencia	Spain
19	Hospital Universitario Lozano Blesa	Zaragoza	Spain