Breast Neoplasm Malignant FemalePhase 2OLTNCT06938724
Omission of Local Therapies in Women Patients With HER2-positive or Triple-negative Breast Cancer
A Phase 2 study testing Omission of local therapies in people with Breast Neoplasm Malignant Female, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasm Malignant Female
- What is being tested?
- Omission of local therapies
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 152 participants
- Where
- 1 siteItaly
- Study dates
- 25 Jul 2025to 25 Jul 2035
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- One of the inclusion criteria missed.
- Residual ductal carcinoma in situ (DCIS) at VABB and/or surgery.
- Bilateral synchronous breast cancer.
- Previous malignancy within 5 years.
- BRCA1-2, PALB2 or p53 proven mutation carrier (VUS are exclusion criteria as well).
- Patients unable to perform regular follow up.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Nazionale Tumori Milano
Milan, 20133
Massimiliano Gennaro, MD, +390223903246, massimiliano.gennaro@istitutotumori.mi.it
About this study
Official title: Omission of Local Therapies in Women Patients With HER2-positive or Triple-negative Breast Cancer: A Two Arm, Phase 2, Non-inferiority Trial for Surveillance in Maximum Responders to Neoadjuvant Systemic Therapy
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.
Read the 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
- Being tested
- Omission of local therapies
- Keywords
- Surveillance for breast cancer relapses, Omission of local therapies, Omission of surgery, Omission of radiotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omission of local therapiesOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Other: Omission of local therapies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Events-free survival (EFS) for each study arm.
Events considered are: local recurrence, distant metastases, or death, whichever will occur first.
Measured: 5 years
Secondary outcomes (1)
Time to rescue surgery
Delayed of treatment in case of local-regional disease reappearance
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2025
- Study start25 Jul 2025
- Primary completion25 Jul 2035 (estimated)
- Study completion25 Jul 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast Neoplasm Malignant FemaleStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 152 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Massimiliano Gennaro, MD, Principal investigator, Fondazione IRCCS Istituto Nazionale Tumori Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06938724
- Sponsor's protocol ID
- INT 246-24
- Acronym
- OLT
- Status last verified
- May 2025
- First submitted
- 7 Apr 2025
- Last updated
- 15 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36306810van 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.
PubMed 36892723
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Omission of Local Therapies in Women Patients With HER2-positive or Triple-negative Breast Cancer: A Two Arm, Phase 2, Non-inferiority Trial for Surveillance in Maximum Responders to Neoadjuvant Systemic Therapy
- ClinicalTrials.gov ID
- NCT06938724
- Acronym / sponsor ID
- OLT / INT 246-24
- Conditions
- Breast Neoplasm Malignant Female
- Keywords
- Surveillance for breast cancer relapses, Omission of local therapies, Omission of surgery, Omission of radiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 152 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- 25 Jul 2025 (actual)
- Primary completion
- 25 Jul 2035 (estimated)
- Study completion
- 25 Jul 2035 (estimated)
- First posted
- 22 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| A Omission of Surgery | Experimental | Other: Omission of local therapiesArm 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). |
| B Omission of Radiotherapy | Experimental | Other: Omission of local therapiesArm 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (6 listed)
- One of the inclusion criteria missed.
- Residual ductal carcinoma in situ (DCIS) at VABB and/or surgery.
- Bilateral synchronous breast cancer.
- Previous malignancy within 5 years.
- BRCA1-2, PALB2 or p53 proven mutation carrier (VUS are exclusion criteria as well).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Omission of local therapiesOmission 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. | Other | A Omission of Surgery, B Omission of Radiotherapy |
Primary outcome
Events-free survival (EFS) for each study arm.
Time frame: 5 years
Events considered are: local recurrence, distant metastases, or death, whichever will occur first.
1 secondary outcome
Time to rescue surgery
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2025.
- Background: PubMed 36306810Kuerer 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.
- Background: PubMed 36892723van 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Massimiliano Gennaro, MD principal investigator
Fondazione IRCCS Istituto Nazionale Tumori Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Omission of local therapies in people with Breast Neoplasm Malignant Female, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Massimiliano Gennaro, MD (+390223903246, massimiliano.gennaro@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Events-free survival (EFS) for each study arm. (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06938724, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2025.