Preoperative Study With Trastuzumab, Pertuzumab and Letrozole in Breast Cancer Patients Sensitive to Hormonal Therapy

NCT ID: NCT02411344

Last Updated: 2018-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2018-01-12

Brief Summary

The purpose of this study is to evaluate the activity of molecular response in endocrine sensitive breast cancer HER2+/HR+ patients treated with Pertuzumab-trastuzumab plus Ietrozole.

Detailed Description

The purpose of this study is:

• to evaluate the rate of pathologic complete response (pCR), as defined as complete disappearance of invasive tumor in breast and axillary nodes.
• to estimate the percentage of clinical objective responses (cOR) (complete plus partial) in the breast, as assessed by ultrasonography (US)
• to estimate the percentage of breast conservative surgery
• to evaluate the safety profile
• To perform correlative biomarker analyses

Conditions

Endocrine Sensitive HER2+/HR+ Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pertuzumab, Trastuzumab, Letrozole

Group Type: EXPERIMENTAL

Pertuzumab

Intervention Type: DRUG

• Pertuzumab 840 mg loading dose iv on day one, followed by 420 mg iv every 3 weeks for 5 cycles
• Trastuzumab 8 mg/kg loading dose iv on day 2, followed by 6 mg/kg iv on day 2 of each subsequent 3 weekly cycle
• Letrozole 2.5 mg daily p.o. for five 21-day cycles (to be continued until surgery).

Interventions

Pertuzumab

• Pertuzumab 840 mg loading dose iv on day one, followed by 420 mg iv every 3 weeks for 5 cycles
• Trastuzumab 8 mg/kg loading dose iv on day 2, followed by 6 mg/kg iv on day 2 of each subsequent 3 weekly cycle
• Letrozole 2.5 mg daily p.o. for five 21-day cycles (to be continued until surgery).

Intervention Type: DRUG

Other Intervention Names

Perjeta

Eligibility Criteria

Inclusion Criteria

• primary diagnosis of infiltrating breast cancer
• HR positivity (ER ≥ 10% and/or PgR ≥10%) and HER2 positivity (IHC 3+ or FISH/CISH amplification), as assessed by local laboratory.
• Stage II-IIIA
• age >18 yrs
• ECOG Performance Status 0-1
• Postmenopausal status, defined by at least one of the following:

60 years of age; < 60 years of age and amenorrheic for >/=12 months prior to day 1 < 60 years of age, without a uterus, and luteinizing hormone (LH) and follicle stimulating hormone (FSH) values within postmenopausal range Prior bilateral oophorectomy Prior radiation castration with amenorrhea for at least 6 months

• Cardiac ejection fraction within the institutional range of normal (as measured by echocardiogram or MUGA scan).
• Normal organ and marrow function as defined below:

(leukocytes >=3000/mcL; absolute neutrophil count >=1,500/mcL; platelets >=100,000/mcL; total bilirubin within 1.25 x normal institutional limits (with the exception of Gilbert's syndrome); AST (SGOT)/ALT(SGPT) within 1.25 x institutional upper limit of normal creatinine within normal institutional limits

• Availability of tumor tissue suitable for biological and molecular examination before starting primary treatment
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Stage IIIB, IIIC, and inflammatory breast cancer
• Stage IV breast cancer
• Prior treatment with chemotherapy, endocrine therapy or radiotherapy. Prior treatment with HER2 targeting therapies
• LVEF below the ULN
• Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) grade II or higher, or serious cardiac arrhythmia requiring medication.
• Received any investigational treatment within 4 weeks of study start.
• Subjects with known infection with HIV, HBV, HCV
• Known hypersensitivity to any of the study drugs or excipients.
• Dyspnoea at rest or other disease requiring continuous oxygen therapy.
• Psychiatric illness/social situations that would limit compliance with study requirements
• Subjects assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Association for Translational Research in Oncology (AS.T.R.O.)

UNKNOWN

Sponsor Role: collaborator

Istituto Oncologico Veneto IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Valentina Guarneri

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Valentina Guarneri, MD; PhD

Role: PRINCIPAL_INVESTIGATOR

Medical Oncology 2, Istituto Oncologico Veneto

Locations

Policlinico Vittorio Emanuele

Catania, CT, Italy

Arcispedale S. Anna

Cona, FE, Italy

Istituto Europeo di Oncologia

Milan, MI, Italy

Istituto Nazionale Tumori

Milan, MI, Italy

Ospedale "Guglielmo da Saliceto"

Piacenza, PC, Italy

Istituto Oncologico Veneto, Oncologia Medica 2

Padua, PD, Italy

Arcispedale S. Maria Nuova

Reggio Emilia, RE, Italy

A. O. U. Santa Maria della Misericordia

Udine, UD, Italy

Countries

Italy

References

Guarneri V, Dieci MV, Bisagni G, Frassoldati A, Bianchi GV, De Salvo GL, Orvieto E, Urso L, Pascual T, Pare L, Galvan P, Ambroggi M, Giorgi CA, Moretti G, Griguolo G, Vicini R, Prat A, Conte PF. De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole: results of the PerELISA neoadjuvant study. Ann Oncol. 2019 Jun 1;30(6):921-926. doi: 10.1093/annonc/mdz055.

Reference Type: DERIVED

PMID: 30778520 (View on PubMed)

Other Identifiers

2013-002662-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AS.T.R.O.BC01-13

Identifier Type: -

Identifier Source: org_study_id