Phase II preoperative study with trastuzumab, pertuzumab and letrozole in patients with breast cancer sensitive to hormonal therapy

Phase 1

• Conditions: Stage II-IIIA operable breast cancer, HER2 positive and hormone receptor-positive, previously untreated; MedDRA version: 14.1Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-002662-40-IT
• Lead Sponsor: AS.T.R.O.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-07-05
• Last Update Posted: 14 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 68

Inclusion Criteria

Patients may be included in the study only if they met all the following criteria
- female patients with 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23

Exclusion Criteria

Patients will be excluded from the study for any of the following reasons
- 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.
- Dyspnea 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 & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: to evaluate the rate of pathologic complete response (pCR), as defined as complete disappearance of invasive tumor in breast and axillary nodes;Secondary Objective: - To estimate the percentage of clinical objective responses (cOR) (complete plus partial) in the breast, as assessed by ultrasonography (US)<br>- To estimate the percentage of breast conservative surgery <br>- To evaluate the safety profile <br>- Correlative biomarker analyses<br>;Primary end point(s): to evaluate the rate of pathologic complete response (pCR), as defined as complete disappearance of invasive tumor in breast and axillary nodes;Timepoint(s) of evaluation of this end point: at the time of surgery

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - To estimate the percentage of clinical objective responses (cOR) (complete plus partial) in the breast, as assessed by ultrasonography (US)<br>- To estimate the percentage of breast conservative surgery <br>- To evaluate the safety profile <br>- Correlative biomarker analyses<br>;Timepoint(s) of evaluation of this end point: at the time of surgery