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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)

Primary Purpose

HER2-positive Breast Cancer, Stage I Breast Cancer

Status

Recruiting

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

Trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination

About this trial

This is an interventional treatment trial for HER2-positive Breast Cancer focused on measuring Breast Cancer, Her2-positive, Pertuzumab, Trastuzumab, Omission surgery

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

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.
A participant is eligible to participate if she is not pregnant, not breastfeeding.
The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
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.
Patient must have known ER and PR status locally determined prior to study entry.
Eligible for taxane therapy.
Willingness of the patient to omit surgery if all criteria are met following neoadjuvant therapy.
Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer.
Breast cancer eligible for primary surgery
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.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Ability and willingness to comply with study visits, treatment, testing and to comply with the protocol.
Have adequate organ function.

Exclusion Criteria:

Has received prior anti-cancer therapy, including investigational agents, or treatment for primary invasive breast cancer.
Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, TDM1 or paclitaxel.
Clinical stage II, III or IV.
History of radiotherapy in the ipsilateral breast or axilla.
History of surgery of the ipsilateral axilla.
Bilateral invasive breast cancer.
Infiltrating lobular carcinoma.
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.
Patients who have undergone sentinel lymph node biopsy prior to study treatment.
Patient has active cardiac disease or a history of cardiac dysfunction
Has an active infection requiring systemic therapy.

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

Sites / Locations

Hospital Clinic de BarcelonaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Omission of surgery

Surgery

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT04578106

First Posted

September 29, 2020

Last Updated

January 23, 2022

Sponsor

Fundacio Clinic Barcelona

Collaborators

SOLTI Breast Cancer Research Group, Roche Pharma AG

1. Study Identification

Unique Protocol Identification Number

NCT04578106

Brief Title

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

Acronym

ELPIS

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 23, 2020 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fundacio Clinic Barcelona

Collaborators

SOLTI Breast Cancer Research Group, Roche Pharma AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HER2-positive Breast Cancer, Stage I Breast Cancer

Keywords

Breast Cancer, Her2-positive, Pertuzumab, Trastuzumab, Omission surgery

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

17 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Omission of surgery

Arm Type

Experimental

Arm Description

Arm Title

Surgery

Arm Type

No Intervention

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

Trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination

Other Intervention Name(s)

Omission of surgery

Intervention Description

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.

Primary Outcome Measure Information:

Title

Description

Time Frame

3 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. A participant is eligible to participate if she is not pregnant, not breastfeeding. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 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. Patient must have known ER and PR status locally determined prior to study entry. Eligible for taxane therapy. Willingness of the patient to omit surgery if all criteria are met following neoadjuvant therapy. Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer. Breast cancer eligible for primary surgery 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. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Ability and willingness to comply with study visits, treatment, testing and to comply with the protocol. Have adequate organ function. Exclusion Criteria: Has received prior anti-cancer therapy, including investigational agents, or treatment for primary invasive breast cancer. Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, TDM1 or paclitaxel. Clinical stage II, III or IV. History of radiotherapy in the ipsilateral breast or axilla. History of surgery of the ipsilateral axilla. Bilateral invasive breast cancer. Infiltrating lobular carcinoma. 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. Patients who have undergone sentinel lymph node biopsy prior to study treatment. Patient has active cardiac disease or a history of cardiac dysfunction Has an active infection requiring systemic therapy. 13. Patients with a history of previous breast cancer are excluded.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Laia Arenas

Phone

93 2275400

Ext

3456

ELPIS@clinic.cat

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Aleix Prat, MD

Organizational Affiliation

Hospital Clinic of Barcelona

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Tomas Pascual, MD

Organizational Affiliation

Hospital Clinic of Barcelona

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital Clinic de Barcelona

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Laia Arenas

Phone

+34 93 227 54 00

elpis@clinic.cat

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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