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

Breast Cancer Clinical Trial

— Opti-HER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01669239
• Other study ID #: SOLTI-1002
• Secondary ID: 2012-001201-24
• Status: Completed
• Phase: Phase 2
• First received: August 9, 2012
• Last updated: October 31, 2017
• Start date: June 2013
• Est. completion date: January 2016

Study information

• Verified date: October 2017
• Source: SOLTI Breast Cancer Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 74 Years

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitario Vall d´Hebron	Barcelona
Spain	Complejo Hospitalario San Pedro de Alcántara	Cáceres
Spain	Hospital Universitari Arnau de Vilanova de Lleida	Lleida
Spain	Centro Integral Oncológico Clara Campal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Clínico San Carlos	Madrid
Spain	Hospital Universitario Puerta de Hierro de Majadahonda	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Son Llàtzer	Palma de Mallorca
Spain	Hospital Universitari Son Espases	Palma de Mallorca
Spain	Hospital Sant Joan de Reus	Reus
Spain	Hospital Sagrado Corazón USP	Sevilla
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Virgen de la Macarena	Sevilla
Spain	Fundación Instituto Valenciano de Oncología	Valencia
Spain	Hospital Arnau de Vilanova de Valencia	Valencia
Spain	Hospital Universitario Lozano Blesa	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
SOLTI Breast Cancer Research Group

Country where clinical trial is conducted

Spain, 

References & Publications (1)

Gavilá J, Llombart A, Guerrero A, Ruíz A, Climent M, Guillem V. Opti-HER HEART: A prospective, multicenter, single-arm, phase II study to evaluate the safety of neoadjuvant liposomal doxorubicin plus paclitaxel, trastuzumab, and pertuzumab in patients with operable HER2-positive breast cancer. Poster session presented at: 35th Annual San Antonio Breast Cancer Symposium (SABCS); 2012 December 4th-8th; San Antonio, Texas, United States.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	pCR in breast (pCRB)		At the time of definitive surgery, an expected average of 23 weeks
Secondary	pCR in breast and axilla (pCRBA)		At the time of definitive surgery, an expected average of 23 weeks
Secondary	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
Secondary	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
Secondary	Breast conservation rate at surgery		At the time of definitive surgery, an expected average of 23 weeks
Secondary	Evaluation of serum biomarkers predictive of cardiotoxicity		Following 12 months after first dose of the study treatment
Secondary	Percentage of patients with grade 3/4 neutropenia (assessed by CTCAE v.4)		Following 12 months after first dose of the study treatment
Secondary	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
Secondary	Dose reductions due to treatment toxicity (assessed by CTCAE v.4)		Following 12 months after first dose of the study treatment
Secondary	Dose delays due to treatment toxicity (assessed by CTCAE v.4)		Following 12 months after first dose of the study treatment
Secondary	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

External Links

•   SOLTI Breast Cancer Research Group