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

A Phase II Study of NEOADjuvant Aromatase Inhibitor and Pertuzumab/Trastuzumab (NEOADAPT)

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.

Study Overview

• Status: Unknown
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Exemestane; Drug: Letrozole; Drug: Anastrozole; Drug: Leuprolide Acetate; Drug: Pertuzumab; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Southeastern Regional Medical Center
  • Illinois
    • Zion, Illinois, United States, 60099
      • Cancer Treatment Centers of America at Midwestern Regional Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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

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: Neoadjuvant Biological Therapy; 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)

Drug: Exemestane; Aromatase inhibitor; Other Names: Aromasin; Drug: Letrozole; Aromatase inhibitor; Other Names: Femara; Drug: Anastrozole; Aromatase inhibitor; Other Names: Arimidex; Drug: Leuprolide Acetate; Luteinizing Hormone-Releasing Hormone agonist; Other Names: Lupron; Lupron Depot; Drug: Pertuzumab; Monoclonal antibody (HER2/neu receptor antagonist); Other Names: Perjeta; Drug: Trastuzumab; Monoclonal antibody (HER2/neu receptor antagonist); Other Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evidence of Pathological Response	The presence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. Pathological complete response (pCR) is defined as the absence of residual invasive cancer.	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Treatment	Median number of days between Day 0 (first treatment of trastuzumab and pertuzumab) and three weeks after the last dose of neoadjuvant trastuzumab and pertuzumab on treatment protocol.	One year
Evidence of Radiographic Response	Change in dimensions (millimeters) of target lesions (along long axis) and non-target lesions (along long axis for non-lymphatic lesions and short axis for lymph nodes) as observed by Magnetic Resonance Imaging and quantified by modified RECIST 1.1 criteria.	Assessed every 12 weeks up to one year
Measurement of Left Ventricular Ejection Fraction (LVEF)	Determination of cardiac function as measured by echocardiogram or multi-gated acquisition scan (MUGA).	Assessed every 12 weeks up to one year
Mammaprint Genomic Analysis	Mammaprint will estimate the risk level of the subject's tumor.	One year or up to 3 months after definitive surgery

Collaborators and Investigators

• Sponsor: Midwestern Regional Medical Center
• Investigators: Principal Investigator: Eugene Ahn, MD, Midwestern Regional Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: February 4, 2016
• First Submitted That Met QC Criteria: February 18, 2016
• First Posted (Estimate): February 24, 2016

Study Record Updates

• Last Update Posted (Actual): September 28, 2018
• Last Update Submitted That Met QC Criteria: September 27, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Trastuzumab; Letrozole; Leuprolide; Anastrozole; Exemestane; Pertuzumab
• Other Study ID Numbers: MZ2016006; ML30001 (Other Identifier: Genentech, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED