Omission of Local Therapies in Women Patients With HER2-positive or Triple-negative Breast Cancer (OLT)
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Massimiliano Gennaro, MD
- Phone Number: +390223903246
- Email: massimiliano.gennaro@istitutotumori.mi.it
Study Contact Backup
- Name: Kiara Muca
- Phone Number: +390223903908
- Email: kiara.muca@istitutotumori.mi.it
Study Locations
-
-
-
Milan, Italy, 20133
- Recruiting
- Fondazione IRCCS Istituto Nazionale Tumori Milano
-
Contact:
- Massimiliano Gennaro, MD
- Phone Number: +390223903246
- Email: massimiliano.gennaro@istitutotumori.mi.it
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: 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).
|
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. |
|
Experimental: 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).
|
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Time to rescue surgery
Time Frame: 5 years
|
Delayed of treatment in case of local-regional disease reappearance
|
5 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Massimiliano Gennaro, MD, Fondazione IRCCS Istituto Nazionale Tumori Milan
Publications and helpful links
General 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- INT 246-24
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.