Omission of Local Therapies in Women Patients With HER2-positive or Triple-negative Breast Cancer

NCT06938724 | Recruiting Phase 2 DMC

• 1 other identifier: INT 246-24
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

HER2-positive and Triple-negative are subtypes of breast cancer more sensitive to systemic therapies, where the complete pathological response rate may be higher than 50%. This gave rise to doubts about the usefulness of traditional local treatments for such responders. Omission of surgery after vacuum assisted breast biopsy (VABB) as well omission of radiotherapy after conservative surgery would now seem to be reasonable alternatives to standard care for highly selected patients, in whom systemic treatments have provided the maximum response.

Conditions

Breast Neoplasm Malignant Female

Keywords

Surveillance for breast cancer relapses; Omission of local therapies; Omission of surgery; Omission of radiotherapy

Outcome Measures

Primary Outcomes (1)

• Events-free survival (EFS) for each study arm.

  Events considered are: local recurrence, distant metastases, or death, whichever will occur first.

  5 years

Secondary Outcomes (1)

• Time to rescue surgery

  5 years

Study Arms (2)

A Omission of Surgery

EXPERIMENTAL

Arm A will evaluate the omission of surgery in unifocal T1-2 clinically N0, M0 patients who will demonstrate maximum response after neoadjuvant systemic treatment (i.e. whole breast irradiation only).

Other: Omission of local therapies

B Omission of Radiotherapy

EXPERIMENTAL

Arm B will evaluate the omission of radiotherapy in unifocal T1-2, N1, M0 patients with complete pathological response proved by standard conservative surgical treatment (i.e. conservative surgery only and surgical staging of axilla).

Other: Omission of local therapies

Interventions

Omission of local therapies OTHER

Omission of surgery (arm A) or radiotherapy (arm B) in those patients who have had the maximum response by neoadjuvant treatments. Maximum responders are those patients with no evidence of residual disease after neoadjuvant treatment at imaging -including mammography, US evaluation and contrast imaging procedures (MRI and/or CEM)-, confirmed by VABB on marked site of ascertained lesion. This study is open to all patients with T1-2, N0-1, M0 HER2-positive or triple negative breast cancer, treated with neoadjuvant systemic treatment, irrespective of treatments delivered.

A Omission of Surgery; B Omission of Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ≥ 18y.
• Initial diagnosis of unifocal HER2-positive (regardless of HR status) or Triple-negative (HR positivity lower than 10% is allowed) T1-2, N0-1, M0 breast cancer.
• Treated with neoadjuvant systemic treatment according to the center recommendations.
• Maximum responders and/or complete pathological response proved by surgery.
• Scheduled for breast conservation.
• Giving specific informed consent.

You may not qualify if:

• Residual ductal carcinoma in situ (DCIS) at VABB and/or surgery.
• Bilateral synchronous breast cancer.
• Previous malignancy within 5 years.
• Patients unable to perform regular follow up.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale Tumori Milano

Milan, 20133, Italy

RECRUITING

Related Publications (2)

• Kuerer HM, Smith BD, Krishnamurthy S, Yang WT, Valero V, Shen Y, Lin H, Lucci A, Boughey JC, White RL, Diego EJ, Rauch GM; Exceptional Responders Clinical Trials Group. Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2022 Dec;23(12):1517-1524. doi: 10.1016/S1470-2045(22)00613-1. Epub 2022 Oct 25.

  PMID: 36306810 BACKGROUND

• van Hemert AKE, van Olmen JP, Boersma LJ, Maduro JH, Russell NS, Tol J, Engelhardt EG, Rutgers EJT, Vrancken Peeters MTFD, van Duijnhoven FH. De-ESCAlating RadioTherapy in breast cancer patients with pathologic complete response to neoadjuvant systemic therapy: DESCARTES study. Breast Cancer Res Treat. 2023 May;199(1):81-89. doi: 10.1007/s10549-023-06899-y. Epub 2023 Mar 9.

  PMID: 36892723 BACKGROUND

Study Officials

• Massimiliano Gennaro, MD

  Fondazione IRCCS Istituto Nazionale Tumori Milan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Massimiliano Gennaro, MD

CONTACT

+390223903246; massimiliano.gennaro@istitutotumori.mi.it

Kiara Muca

CONTACT

+390223903908; kiara.muca@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is open to all patients with T1-2, N0-1, M0 HER2-positive or triple negative breast cancer, treated with neoadjuvant systemic treatment, irrespective of treatments delivered. The aim of the study is to evaluate outcome in maximum responders to neoadjuvant systemic therapies, when surgery or whole breast irradiation are alternatively omitted. Arm A will evaluate the omission of surgery in unifocal T1-2 clinically N0, M0 patients who will demonstrate maximum response after neoadjuvant systemic treatment (i.e. whole breast irradiation only). Arm B will evaluate the omission of radiotherapy in patients with complete pathological response proved by standard conservative surgical treatment (i.e. conservative surgery only).

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: April 22, 2025
• Study Start: July 25, 2025
• Primary Completion (Estimated): July 25, 2035
• Study Completion (Estimated): July 25, 2035
• Last Updated: September 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)