NEOADjuvant Aromatase Inhibitor and Pertuzumab/Trastuzumab for Women With Breast Cancer (NEOADAPT)

Midwestern Regional Medical Center

Status and phase

Unknown

Phase 2

Conditions

Breast Neoplasms

Treatments

Drug: Letrozole

Drug: Leuprolide Acetate

Drug: Pertuzumab

Drug: Trastuzumab

Drug: Exemestane

Drug: Anastrozole

Study type

Interventional

Funder types

Other

Identifiers

NCT02689921

MZ2016006

ML30001 (Other Identifier)

Details and patient eligibility

About

This is a prospective, single-arm, phase II study of 32 evaluable patients treated with NEOADjuvant Aromatase inhibitor and Pertuzumab/Trastuzumab (NEOADAPT) without chemotherapy for hormone receptor positive (HR+), [i.e. Estrogen Receptor positive (ER+) and/or Progesterone Receptor positive (PR+)] HER2+ localized, non-metastatic stage I - IIb breast cancer.

Enrollment

7 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Ability to provide signed, written informed consent
Histologically or cytologically confirmed non-metastatic adenocarcinoma of the breast (stage I-II)
Candidate for curative-intent treatment
ER+ and/or PR+ and HER2-positive (Fluorescence In Situ Hybridization-positive or 3+ by Immunohistochemistry staining)
Life expectancy greater than 5 years
Left Ventricular Ejection Fraction > 50% at baseline (within 30 days of day 0)
Eastern Cooperative Oncology Group performance status ≤2
Absolute Neutrophil Count >1000/µL
Platelets ≥50,000/µL
Hemoglobin >8.0 g/dL,
Creatinine ≤3.0 x upper limit of normal (ULN)
Bilirubin ≤3.0 x ULN
Aspartate aminotransferase or Alanine aminotransferase <5.0 x ULN
Negative serum pregnancy test for women <12 months after the onset of menopause unless surgically sterilized
Agreement by women of childbearing potential and male participants with partners of childbearing potential to use a "highly effective", non-hormonal form of contraception or two "effective" forms of non-hormonal contraception by the patient and/or partner.

Exclusion criteria

Active infection
Presence of known metastases (stage IV disease)
Pregnant or lactating women
Prior chemotherapy or radiation therapy for the primary breast cancer
Concomitant malignancies or previous malignancies within the last 5 years except adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary or metabolic disease including diabetes, wound healing disorders, ulcers or bone fractures)
Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipated need for major surgery during the course of study treatment
Current known infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV) or Hepatitis C Virus (HCV)
Receipt of intravenous antibiotics for infection within 14 days prior to receiving study treatment
Current chronic daily treatment with corticosteroids (dose >10 mg/day methylprednisolone equivalent) except inhaled steroids
Known hypersensitivity to any of the study drugs
Assessment by the investigator to be unable or unwilling to comply with the requirements of the protocol

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

7 participants in 1 patient group

Neoadjuvant Biological Therapy

Experimental group

Description:

Subjects will receive an aromatase inhibitor for the duration of the study \[exemestane (tablet, oral, 25 mg/day), letrozole (tablet, oral, 2.5 mg/day) or anastrozole (tablet, oral, 1 mg/day)\]. Premenopausal subjects will receive leuprolide acetate (11.25 mg, intramuscular injection, 3-month intervals). Pertuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 840 mg, infused over 60-90 minutes; subsequent cycles: 420 mg, infused over 30-60 minutes). Trastuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 8 mg/kg, infused over 60-90 minutes; subsequent cycles: 6 mg/kg, infused over 30-60 minutes)