Clinical trial NCT02411344: Preoperative Study With Trastuzumab, Pertuzumab and Letrozole in Breast Cancer Patients Sensitive to Hormonal Therapy
Official title: PERtuzumab-trastuzumab Plus lEetrozoLe In Endocrine Sensitive Breast Cancer: a Phase II neoAdjuvant Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endocrine Sensitive HER2+/HR+ Breast Cancer
Keywords: HER2+/HR+
breast cancer
Lead sponsor: Istituto Oncologico Veneto IRCCS
Sponsor class: OTHER
Collaborators: name: Association for Translational Research in Oncology (AS.T.R.O.)
First posted: 2015-04-08
Enrollment: 64
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Rate of pathologic complete response
timeFrame: At time of surgery, within 3 weeks from the last i.v. therapy
Secondary outcomes:
measure: Percentage of clinical objective response.
timeFrame: At time of surgery, within 3 weeks from the last i.v. therapy
measure: Rate of Conservative Surgery
timeFrame: At time of surgery, within 3 weeks from the last i.v. therapy
measure: Safety profile assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) To version 4.0 will be used
timeFrame: Every 21-day cycles
measure: Occurrence of mutations in the PIK3CA gene
timeFrame: Within 4 weeks prior to first dose treatment
Other outcomes:
Locations:
city: Catania
country: Italy
facility: Policlinico Vittorio Emanuele
state: CT
city: Cona
country: Italy
facility: Arcispedale S. Anna
state: FE
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: MI
city: Milano
country: Italy
facility: Istituto Nazionale Tumori
state: MI
city: Piacenza
country: Italy
facility: Ospedale "Guglielmo da Saliceto"
state: PC
city: Padova
country: Italy
facility: Istituto Oncologico Veneto, Oncologia Medica 2
state: PD
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova
state: RE
city: Udine
country: Italy
facility: A. O. U. Santa Maria della Misericordia
state: UD
Study officials:
affiliation: Medical Oncology 2, Istituto Oncologico Veneto
name: Valentina Guarneri, MD; PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.