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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by SOLTI Breast Cancer Research Group
Sponsor:
Information provided by (Responsible Party):
SOLTI Breast Cancer Research Group
ClinicalTrials.gov Identifier:
NCT01669239
First received: August 9, 2012
Last updated: October 10, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Breast Cancer
Drug: Liposomal Doxorubicin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by SOLTI Breast Cancer Research Group:

Primary Outcome Measures:
  • Rate of symptomatic (type A) and asymptomatic (type B) cardiac events during the study treatment period [ Time Frame: Following 12 months after first dose of the study treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • pCR in breast (pCRB) [ Time Frame: At the time of definitive surgery, an expected average of 23 weeks ] [ Designated as safety issue: No ]
  • pCR in breast and axilla (pCRBA) [ Time Frame: At the time of definitive surgery, an expected average of 23 weeks ] [ Designated as safety issue: No ]
  • Clinical objective response rate (cORR) in the breast and axilla by RECIST criteria version 1.1 [ Time Frame: At the time of definitive surgery, an expected average of 23 weeks ] [ Designated as safety issue: No ]
  • Residual Cancer Burden (RCB) at surgery following the procedures of the MD Anderson Cancer Center [ Time Frame: At the time of definitive surgery, an expected average of 23 weeks ] [ Designated as safety issue: No ]
  • Breast conservation rate at surgery [ Time Frame: At the time of definitive surgery, an expected average of 23 weeks ] [ Designated as safety issue: No ]
  • Evaluation of serum biomarkers predictive of cardiotoxicity [ Time Frame: Following 12 months after first dose of the study treatment ] [ Designated as safety issue: Yes ]
  • Percentage of patients with grade 3/4 neutropenia (assessed by CTCAE v.4) [ Time Frame: Following 12 months after first dose of the study treatment ] [ Designated as safety issue: Yes ]
  • Time of onset and time of recovery from symptomatic (type A) and asymptomatic (type B) cardiac events (assessed by CTCAE v.4) [ Time Frame: Following 12 months after first dose of the study treatment ] [ Designated as safety issue: Yes ]
  • Dose reductions due to treatment toxicity (assessed by CTCAE v.4) [ Time Frame: Following 12 months after first dose of the study treatment ] [ Designated as safety issue: Yes ]
  • Dose delays due to treatment toxicity (assessed by CTCAE v.4) [ Time Frame: Following 12 months after first dose of the study treatment ] [ Designated as safety issue: Yes ]
  • Number of patients with adverse events and serious adverse events (assessed by CTCAE v.4) [ Time Frame: Following 12 months after first dose of the study treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 83
Study Start Date: June 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Myocet® (liposome-encapsulated doxorubicin)

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01669239

Contacts
Contact: Meritxell Tort +34 933 436 302 m.tort@gruposolti.org

Locations
Spain
Hospital Universitario Vall d´Hebron Recruiting
Barcelona, Spain
Contact: Beatriz Garcia    +34932746000 ext 4691    beatrgarcia@vhebron.net   
Principal Investigator: José Manuel Pérez García         
Hospital Clínic de Barcelona Recruiting
Barcelona, Spain
Contact: Montse Fontanillas    +34 93 2275400 ext 3456    mfontani@clinic.ub.es   
Principal Investigator: Montserrat Muñoz Mateu         
Complejo Hospitalario San Pedro de Alcántara Recruiting
Cáceres, Spain
Contact: Alicia López    +34 927 256 406    ensayosclinicoscaceres@gmail.com   
Principal Investigator: Santiago González         
Hospital Universitari Arnau de Vilanova de Lleida Recruiting
Lleida, Spain
Contact: David Martínez    +34 973 24 81 00 ext 2806    eoncolleida@gmail.com   
Principal Investigator: Serafín Morales         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Rosa Rodriguez    +34 927 256 406    rrnotario@h12o.es   
Principal Investigator: Eva Ciruelos         
Centro Integral Oncológico Clara Campal Recruiting
Madrid, Spain
Contact: Sofia Perea       sofiaperea@hospitaldemadrid.com   
Principal Investigator: María Fernández Abad         
Hospital Universitario Clínico San Carlos Recruiting
Madrid, Spain
Contact: Rosario Alfonso    +34 913303000 ext 7545    alfonsosansegundo@yahoo.es   
Principal Investigator: José Angel García-Saenz         
MD Anderson Cancer Center Madrid Recruiting
Madrid, Spain
Contact: Ana Cortijo       acortijo@mdanderson.es   
Principal Investigator: Antonio González Martín         
Hospital Universitario Puerta de Hierro de Majadahonda Recruiting
Madrid, Spain
Contact: Sandra Cerdeira    +34 91 191 6671    scerdeira.hpth@salud.madrid.org   
Principal Investigator: Blanca Cantos         
Hospital Universitario Virgen de la Arrixaca Recruiting
Murcia, Spain
Contact: Ana Pérez    +34 968 36 93 87    dm.oncoarrixaca@gmail.com   
Principal Investigator: Jerónimo Martínez         
Hospital Son Llàtzer Recruiting
Palma de Mallorca, Spain
Contact: Sabina Soler    +34 871 202 000 ext 1629    ssoler@hsll.es   
Principal Investigator: Isabel Garau         
Hospital Universitari Son Espases Recruiting
Palma de Mallorca, Spain
Contact: Joana Mascaro    +34 871205000 ext 76130    juanam.mascaro@ssib.es   
Principal Investigator: Antoni Avellà         
Hospital Sant Joan de Reus Recruiting
Reus, Spain
Contact: Berta Caballé    977310300 ext 55517    bcaballe@grupsagessa.com   
Principal Investigator: Kepa Amillano         
Hospital Sagrado Corazón USP Recruiting
Sevilla, Spain
Contact: Juan Carlos Quero    +34 954 937 676      
Principal Investigator: Juan Carlos Quero         
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain
Contact: Macarena Cruz    +34 955 013 068    ensayosclinicos.hvr.sspa@juntadeandalucia.es   
Principal Investigator: Rosario González         
Hospital Virgen de la Macarena Recruiting
Sevilla, Spain
Contact: Mª Angeles Lobo    +34 955 01 15 20    oncomacarena@gmail.com   
Principal Investigator: Juan Antonio Virizuela Echaburu         
Hospital Arnau de Vilanova de Valencia Recruiting
Valencia, Spain
Contact: Vicente Alberola    +34 963987700    alberola_vicara@gva.es   
Principal Investigator: Antonio Llombart         
Fundación Instituto Valenciano de Oncología Recruiting
Valencia, Spain
Contact: Lidia Riquelme    +34 961104624    datamanager3@fincivo.org   
Principal Investigator: Joaquín Gavilá Gregori         
Hospital Universitario Lozano Blesa Recruiting
Zaragoza, Spain
Contact: Belén Martín    +34976765746    bmartin.iacs@aragon.es   
Principal Investigator: Raquel Andres         
Sponsors and Collaborators
SOLTI Breast Cancer Research Group
Investigators
Principal Investigator: Joaquín Gavilá Gregori, MD Fundación Instituto Valenciano de Oncología
  More Information

Additional Information:
Publications:
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.

Responsible Party: SOLTI Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT01669239     History of Changes
Other Study ID Numbers: SOLTI-1002, 2012-001201-24
Study First Received: August 9, 2012
Last Updated: October 10, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by SOLTI Breast Cancer Research Group:
Breast Cancer
HER2 positive
Neoadjuvant
Liposomal doxorubicin
Paclitaxel
Trastuzumab
Pertuzumab
Safety

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Doxorubicin
Liposomal doxorubicin
Paclitaxel
Pertuzumab
Trastuzumab
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014