Preoperative Study With Trastuzumab, Pertuzumab and Letrozole in Breast Cancer Patients Sensitive to Hormonal Therapy (PER-ELISA)

PERtuzumab-trastuzumab Plus lEetrozoLe In Endocrine Sensitive Breast Cancer: a Phase II neoAdjuvant Study

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.

Study Overview

• Status: Completed
• Conditions: Endocrine Sensitive HER2+/HR+ Breast Cancer
• Intervention / Treatment: Drug: Pertuzumab

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

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • CT
    • Catania, CT, Italy
      • Policlinico Vittorio Emanuele
  • FE
    • Cona, FE, Italy
      • Arcispedale S. Anna
  • MI
    • Milano, MI, Italy
      • Istituto Europeo Di Oncologia
    • Milano, MI, Italy
      • Istituto Nazionale Tumori
  • PC
    • Piacenza, PC, Italy
      • Ospedale "Guglielmo da Saliceto"
  • PD
    • Padova, PD, Italy, 35128
      • Istituto Oncologico Veneto, Oncologia Medica 2
  • RE
    • Reggio Emilia, RE, Italy
      • Arcispedale S. Maria Nuova
  • UD
    • Udine, UD, Italy
      • A. O. U. Santa Maria della Misericordia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pertuzumab, Trastuzumab, Letrozole	Drug: 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).; Other Names: Perjeta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of pathologic complete response	A pathologic complete response (pCR) is defined the complete absence of infiltrating tumor cells in the breast and in lymph nodes. Residual in situ disease (DCIS) will be included in the pCR category.	At time of surgery, within 3 weeks from the last i.v. therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of clinical objective response.	The Clinical Response will be defined according to RECIST criteria comparing the tumor size (largest tumor diameter) before and after treatment, as assessed by ultrasound examination.	At time of surgery, within 3 weeks from the last i.v. therapy
Rate of Conservative Surgery		At time of surgery, within 3 weeks from the last i.v. therapy
Safety profile assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) To version 4.0 will be used		Every 21-day cycles
Occurrence of mutations in the PIK3CA gene		Within 4 weeks prior to first dose treatment

Collaborators and Investigators

• Sponsor: Istituto Oncologico Veneto IRCCS
• Collaborators: Association for Translational Research in Oncology (AS.T.R.O.)
• Investigators: Principal Investigator: Valentina Guarneri, MD; PhD, Medical Oncology 2, Istituto Oncologico Veneto

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): January 12, 2018
• Study Completion (Actual): January 12, 2018

Study Registration Dates

• First Submitted: March 5, 2015
• First Submitted That Met QC Criteria: April 2, 2015
• First Posted (Estimate): April 8, 2015

Study Record Updates

• Last Update Posted (Actual): September 18, 2018
• Last Update Submitted That Met QC Criteria: September 17, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: breast cancer; HER2+/HR+
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Hypersensitivity; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pertuzumab
• Other Study ID Numbers: AS.T.R.O.BC01-13; 2013-002662-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO