Omission of Surgery in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti-HER2-based Neoadjuvant Therapy (ELPIS)

Omission of Surgery and Sentinel Lymph Node Dissection in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti-HER2-based Neoadjuvant Therapy

This is a prospective, single arm, open-label, unicenter, exploratory study in women with primary operable HER2-positive, HER2-enriched/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression), to evaluate the omission of surgery and sentinel lymph node dissection in patients with HER2-E and ERBB2 high breast cancer who achieving a complete response following standard anti-HER2-based neoadjuvant therapy with paclitaxel/trastuzumab/pertuzumab. The primary trial objective is to estimate the loco-regional invasive disease-free survival at 3-year of patients who achieve a complete response based on imaging (i.e. Magnetic resonance imaging) and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.

Study Overview

• Status: Recruiting
• Conditions: Stage I Breast Cancer; HER2-positive Breast Cancer
• Intervention / Treatment: Biological: Trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination

• Study Type: Interventional
• Enrollment (Anticipated): 17
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laia Arenas; Phone Number: 3456 93 2275400; Email: ELPIS@clinic.cat

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínic de Barcelona
    • Contact: Laia Arenas; Phone Number: +34 93 227 54 00; Email: elpis@clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female participants who are at least 40 years of age on the day of signing the informed consent form with histologically confirmed diagnosis of breast cancer.
2. A participant is eligible to participate if she is not pregnant, not breastfeeding.
3. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

4. Histologically confirmed invasive adenocarcinoma of the breast, with all of the following characteristics:

   • HER2-positive status by local determination according to 2018 ASCO/CAP guidelines.
   • PAM50 HER2-enriched subtype and ERBB2-high as predefined cutoff as per central determination.
   • Unifocal invasive carcinoma: only 1 invasive focus can be observed (the tumor focus containing or not containing an in situ component)
   • Tumor largest diameter ≤4 cm as defined by breast MRI.
   • No nodal involvement (i.e. cN0). Any suspicious axillary node by ultrasound must be biopsied. If the biopsy or the FNA is negative of tumor cells, patient is eligible.
   • No evidence of distant metastasis (M0) by routine clinical assessment.
5. Patient must have known ER and PR status locally determined prior to study entry.
6. Eligible for taxane therapy.
7. Willingness of the patient to omit surgery if all criteria are met following neoadjuvant therapy.
8. Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer.
9. Breast cancer eligible for primary surgery
10. Have provided archival tumor tissue sample or newly obtained core. Formalin-fixed,paraffin embedded (FFPE) tissue blocks are mandatory. Available pre-treatment FFPE core biopsy evaluable for PAM50 or possibility to obtain one.
11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
12. Ability and willingness to comply with study visits, treatment, testing and to comply with the protocol.
13. Have adequate organ function.

Exclusion Criteria:

1. Has received prior anti-cancer therapy, including investigational agents, or treatment for primary invasive breast cancer.
2. Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, TDM1 or paclitaxel.
3. Clinical stage II, III or IV.
4. History of radiotherapy in the ipsilateral breast or axilla.
5. History of surgery of the ipsilateral axilla.
6. Bilateral invasive breast cancer.
7. Infiltrating lobular carcinoma.
8. Multicentric or multifocal breast cancer, defined as the presence of two or more foci of cancer in the same or different quadrants of the same breast.
9. Patients who have undergone sentinel lymph node biopsy prior to study treatment.
10. Patient has active cardiac disease or a history of cardiac dysfunction
11. Has an active infection requiring systemic therapy.

13. Patients with a history of previous breast cancer are excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omission of surgery; Neoadjuvant period: paclitaxel IV 80mg/m2 every week for 12 weeks with trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination (FDC) (a loading dose of 1200 mg pertuzumab and 600 mg trastuzumab followed by a maintenance dose of 600 mg pertuzumab and 600 mg trastuzumab once every 3 weeks) for 5 cycles. Adjuvant period: If no invasive tumor cells and no in situ disease are identified in the stereotactic-guided VAB,patients will be eligible to omit loco-regional surgery. Whole breast radiotherapy without nodal radiotherapy will then be performed. Trastuzumab and pertuzumab FDC will be continued to complete 1 year of treatment and adjuvant endocrine therapy will be indicated according to hormonal receptor status by IHC.	Biological: Trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination; After 13 weeks of neoadjuvant treatment, a breast MRI will be performed. If a complete response is observed on breast MRI, patients will undergo a stereotactic-guided VAB of the marker area to obtain 12 cylinders of breast parenchyma, which is equivalent to 2 grams of tissue. If no invasive tumor cells and no in situ disease are identified in the stereotactic-guided VAB, patients will be eligible to omit loco-regional surgery.; Other Names: Omission of surgery
No Intervention: Surgery; Neoadjuvant period: paclitaxel IV 80mg/m2 every week for 12 weeks with trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination (FDC) (a loading dose of 1200 mg pertuzumab and 600 mg trastuzumab followed by a maintenance dose of 600 mg pertuzumab and 600 mg trastuzumab once every 3 weeks) for 5 cycles. Surgery: If invasive tumor cells and/or in situ disease are identified, patients will undergo surgery. Adjuvant period: All patients will continue with Trastuzumab-emtansine (T-DM1) completing 1 year of treatment (14 cycles) and adjuvant endocrine therapy will be indicated according to hormonal receptor status by IHC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the possibility of omission of surgery and sentinel lymph node dissection in clinically low-risk HER2-positive breast cancer with high HER2 addiction and a complete response following standard neoadjuvant chemotherapy and dual HER2 blockade.	To estimate the loco-regional invasive disease-free survival (LR-IDFS) at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.	3 years

Collaborators and Investigators

• Sponsor: Fundacio Clinic Barcelona
• Collaborators: Roche Pharma AG; SOLTI Breast Cancer Research Group
• Investigators: Principal Investigator: Aleix Prat, MD, Hospital Clinic of Barcelona; Principal Investigator: Tomas Pascual, MD, Hospital Clinic of Barcelona

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: September 29, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): January 25, 2022
• Last Update Submitted That Met QC Criteria: January 23, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Breast Cancer; Trastuzumab; Pertuzumab; Her2-positive; Omission surgery
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Pertuzumab
• Other Study ID Numbers: HCB-ONC001 (ML41519)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No