Clinical trial NCT01669239: Study of Neoadjuvant Myocet®, Paclitaxel, Pertuzumab, and Trastuzumab in HER2-positive Breast Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast Cancer
HER2 positive
Neoadjuvant
Liposomal doxorubicin
Paclitaxel
Trastuzumab
Pertuzumab
Safety
Lead sponsor: SOLTI Breast Cancer Research Group
Sponsor class: OTHER
First posted: 2012-08-20
Enrollment: 83
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Rate of symptomatic (type A) and asymptomatic (type B) cardiac events during the study treatment period
timeFrame: Following 12 months after first dose of the study treatment
Secondary outcomes:
measure: pCR in breast (pCRB)
timeFrame: At the time of definitive surgery, an expected average of 23 weeks
measure: pCR in breast and axilla (pCRBA)
timeFrame: At the time of definitive surgery, an expected average of 23 weeks
measure: Clinical objective response rate (cORR) in the breast and axilla by RECIST criteria version 1.1
timeFrame: At the time of definitive surgery, an expected average of 23 weeks
measure: Residual Cancer Burden (RCB) at surgery following the procedures of the MD Anderson Cancer Center
timeFrame: At the time of definitive surgery, an expected average of 23 weeks
measure: Breast conservation rate at surgery
timeFrame: At the time of definitive surgery, an expected average of 23 weeks
measure: Evaluation of serum biomarkers predictive of cardiotoxicity
timeFrame: Following 12 months after first dose of the study treatment
measure: Percentage of patients with grade 3/4 neutropenia (assessed by CTCAE v.4)
timeFrame: Following 12 months after first dose of the study treatment
measure: Time of onset and time of recovery from symptomatic (type A) and asymptomatic (type B) cardiac events (assessed by CTCAE v.4)
timeFrame: Following 12 months after first dose of the study treatment
measure: Dose reductions due to treatment toxicity (assessed by CTCAE v.4)
timeFrame: Following 12 months after first dose of the study treatment
measure: Dose delays due to treatment toxicity (assessed by CTCAE v.4)
timeFrame: Following 12 months after first dose of the study treatment
measure: Number of patients with adverse events and serious adverse events (assessed by CTCAE v.4)
timeFrame: Following 12 months after first dose of the study treatment
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d´Hebron
city: Cáceres
country: Spain
facility: Complejo Hospitalario San Pedro de Alcántara
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro de Majadahonda
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llàtzer
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Espases
city: Reus
country: Spain
facility: Hospital Sant Joan de Reus
city: Sevilla
country: Spain
facility: Hospital Sagrado Corazón USP
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Sevilla
country: Spain
facility: Hospital Virgen de la Macarena
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Lozano Blesa
Study officials:
affiliation: Fundación Instituto Valenciano de Oncología
name: Joaquín Gavilá Gregori, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Gavila J, Oliveira M, Pascual T, Perez-Garcia J, Gonzalez X, Canes J, Pare L, Calvo I, Ciruelos E, Munoz M, Virizuela JA, Ruiz I, Andres R, Perello A, Martinez J, Morales S, Marin-Aguilera M, Martinez D, Quero JC, Llombart-Cussac A, Prat A. Safety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial. BMC Med. 2019 Jan 9;17(1):8. doi: 10.1186/s12916-018-1233-1.