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

NCT ID: NCT06938724

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-25
• Study Completion Date: 2035-07-25

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.

Detailed Description

This is a prospective phase 2 non-randomized non-inferiority trial with two independent investigational arms. In each arm a 2-stage non-inferiority group-sequential design will be implemented; the overall sample per arm is of 76 patients, 43 of which will be recruited at the first stage. For each arm a futility evaluation is foreseen at the first stage, the results of which will be presented to an independent Data Safety and Monitoring Committee (iDSMC) (see "Statistical analyses" paragraph).

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). Patients candidate to arm A, who refuse the omission of surgery and then operated, are eligible for arm B if complete pathological response is confirmed after standard surgical treatment. Moreover, patients who refuse VABB and N1 patients with complete pathological response confirmed by partial mastectomy and surgical staging of axilla (SLNB and or TAD) are also eligible for arm B. Arm B patients must have confirmed complete pathological response by local-regional surgery. Therefore, omission of radiotherapy will be ultimately offered to a cohort of patients with T1-2, N0-1, M0 breast cancer conservatively operated, in whom complete pathological response to a neoadjuvant therapies is confirmed on the entire surgical specimen of the tumor bed and of the sampled nodes.

In each study arm non inferiority of 5-year EFS will be tested against historical data. No between arms statistical comparison is foreseen.

Conditions

Breast Neoplasm Malignant Female

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A Omission of Surgery

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).

Group Type: EXPERIMENTAL

Omission of local therapies

Intervention Type: 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.

B Omission of Radiotherapy

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).

Group Type: EXPERIMENTAL

Omission of local therapies

Intervention Type: 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.

Interventions

Omission of local therapies

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

• Residual ductal carcinoma in situ (DCIS) at VABB and/or surgery.
• Bilateral synchronous breast cancer.
• Previous malignancy within 5 years.

Exclusion Criteria

• Patients unable to perform regular follow up.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Massimiliano Gennaro, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale Tumori Milan

Locations

Fondazione IRCCS Istituto Nazionale Tumori Milano

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Massimiliano Gennaro, MD

Role: CONTACT

massimiliano.gennaro@istitutotumori.mi.it

+390223903246

Kiara Muca

Role: CONTACT

kiara.muca@istitutotumori.mi.it

+390223903908

Facility Contacts

Massimiliano Gennaro, MD

Role: primary

massimiliano.gennaro@istitutotumori.mi.it

+390223903246

References

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.

Reference Type: BACKGROUND

PMID: 36306810 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36892723 (View on PubMed)

Other Identifiers

INT 246-24

Identifier Type: -

Identifier Source: org_study_id