Preoperative Radiation Therapy and Immediate Breast Reconstruction

NCT06739655 | Recruiting

• 1 other identifier: CTO23023GZA
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 6

Brief Summary

The goal of this phase III randomized controlled trial (PRADAIIBE) is to assess if preoperative radiation therapy (Preop-RT) combined with immediate breast reconstruction (IBR) can safely improve both aesthetic and quality of life outcomes in breast cancer patients, compared to the standard of care (SoC) therapy consisting of post-mastectomy radiation therapy (PMRT) and delayed/immediate breast reconstruction, in a population of breast cancer patients with an indication of mastectomy and PMRT. The following hypotheses and outcomes will be assessed at the primary endpoint of 1 year of follow-up:

• Efficacy: Does Preop-RT+IBR lead to a higher BREAST-Q satisfaction with breasts score (primary endpoint), EQ-5D-5L VAS score , EQ-5D-5L Index score, AIS-Total Aesthetic Score, or a shorter treatment duration compared to SoC?
• Safety: Does Preop-RT+IBR lead to an increase in adverse events (general or surgical), a lower rate of pathologic Complete Response (pCR), or worse survival outcomes compared to SoC? \[Note: this study was not powered as a non-inferiority trial, all outcomes will be pooled internationally with parallel studies\] Eligible and consenting participants will undergo screening and baseline assessments. They will then be randomised between experimental (Preop-RT+IBR) and control (SoC) groups, in a 1:1 stratified variable block size design. Follow-up will take place at 3 months, 1, 2, 5, and 10 years after the last study treatment. At baseline and during each follow-up visit each participant will complete the Breast Q 'satisfaction with breasts' and EQ-5D-5L scales, photographs will be taken. During follow-up pCR will be assessed if applicable, adverse events will be registered, and oncological follow-up will be recorded.

Conditions

Breast Carcinoma; Breast Adenocarcinoma; Cancer; Neoplasm; Breast Neoplasms

Keywords

Breast cancer; Radiotherapy; PRADA; Breast reconstruction; BreastQ; QoL; Skin Sparing Mastectomy; Mastectomy; Breast surgery; radiation therapy; Preoperative radiation therapy; Preoperative RT; Cosmesis; Breast satisfaction; Immediate Breast Reconstruction

Outcome Measures

Primary Outcomes (1)

• Patient's satisfaction with breasts.

  Operationalisation (measurement variable): The satisfaction with breasts outcome variable is operationalised through the "satisfaction with breasts" scale from the BREAST-Q (v2) 'Reconstruction', 'Breast Conserving Treatment', or 'Mastectomy' modules (as applicable). The answers from the questionnaire are then transformed into a 'BREAST-Q Score', using the provided conversion scales.(3) The BREAST-Q score can range from 0 to100. Analysis metric: The transformed value of the BREAST-Q score will be used for analysis. Method of aggregation: Mean, SD, median, IQR, and range will be reported. For comparisons and estimands, please refer to the SAP.

  Measured at 3 months, 1year, 2 years, 5 years and 10 years after last locoregional treatment. Primary endpoint: 1 year after LST.

Secondary Outcomes (7)

• Quality of Life (EQ-5D-5L VAS score)

  A baseline assessment is performed during the screening visit, followed by repeated measurements during the IMFU (if applicable), 3M, 1Y, 2Y, 5Y, and 10Y follow-up visits.

• Quality of Life (Index score)

  A baseline assessment is performed during the screening visit, followed by repeated measurements during the IMFU (if applicable), 3M, 1Y, 2Y, 5Y, and 10Y follow-up visits.

• Breast cosmesis, objective assessment (AIS - TAS)

  Photographs are taken during the screening visit, followed by repeated photographs during the IMFU (if applicable), 3M, 1Y, 2Y, 5Y, and 10Y follow-up visits. Expert panel assessment will take place at a later moment.

• Frequency and severity of adverse events (General AEs)

  AEs will be assessed and recorded continuously, with explicit querying during all follow-up visits.

• Frequency and severity of adverse events (Surgical AEs)

  AEs will be assessed and recorded continuously, with explicit querying during all follow-up visits.

Other Outcomes (1)

• Oncological survival and time-to-event data

  Oncological TTE data will be registered at 1, 2, 5, and 10 years of follow-up after the last study treatment (LST). However, the exact dates of diagnosis/death will be used.

Study Arms (2)

Standard treatment arm (SoC; PostOperative RT)

ACTIVE COMPARATOR

Treatment in this arm consists of: 1. Mastectomy 2. Immediate or delayed breast reconstruction. 3. Postoperative radiation therapy, according to the SoC as indicated by international guidelines. \[Systemic treatments are not considered as study treatments and will be implemented at the discretion of the treating physician.\]

Radiation: Postoperative radiotherapy; Procedure: Immediate or delayed breast reconstruction

Experimental treatment arm (PreOperative RT)

EXPERIMENTAL

Treatment in this arm consists of: 1. Preoperative radiation therapy (Preop-RT). Preop-RT will be administered according to the same parameters and quality standards as PMRT/WBRT, as indicated by international guidelines. 2. Mastectomy combined with immediate breast reconstruction, after a 2-6 weeks interval. \[Systemic treatments are not considered as study treatments and will be implemented at the discretion of the treating physician.\]

Radiation: Preoperative radiotherapy; Procedure: Immediate breast reconstruction

Interventions

Preoperative radiotherapy RADIATION

In this study patients assigned to the experimental treatment arm will receive preoperative radiation therapy instead of postoperative radiation therapy (PMRT). This preoperative radiation therapy will be administered according to the standard of care (SoC) principles for PMRT and Whole Breast Radiation Therapy (WBRT) as defined by international guidelines.

Also known as: Preop-RT, Neoadjuvant radiation therapy, NART

Experimental treatment arm (PreOperative RT)

Postoperative radiotherapy RADIATION

Standard of care (SoC) postoperative radiotherapy, as defined by international guidelines.

Also known as: Postop-RT, Postmastectomy Radiation Therapy, PMRT, Adjuvant Radiation Therapy, ART

Standard treatment arm (SoC; PostOperative RT)

Immediate breast reconstruction PROCEDURE

In the experimental arm of the PRADAIIBE, the participants will undergo immediate breast reconstruction surgery. This is defined as breast reconstruction taking place at the same time as oncological surgery. Using one of the following primary techniques: 1) Autologous tissue reconstruction ; 2) Breast implant based reconstruction; 3) Combined autologous tissue and breast implant reconstruction. These techniques can take place in a single phase, or in a two-phased (tissue expander) approach. Adjuvant techniques (e.g.: lipofilling, mesh, ADM etc.) could be added.

Also known as: IBR

Experimental treatment arm (PreOperative RT)

Immediate or delayed breast reconstruction PROCEDURE

In the standard arm of the PRADAIIBE, the participants will undergo immediate or delayed breast reconstruction surgery. This is defined as breast reconstruction taking place at the same time as oncological surgery (immediate), or at a later time (delayed). Using one of the following primary techniques: 1) Autologous tissue reconstruction ; 2) Breast implant based reconstruction; 3) Combined autologous tissue and breast implant reconstruction. These techniques can take place in a single phase, or in a two-phased (tissue expander) approach. Adjuvant techniques (e.g.: lipofilling, mesh, ADM etc.) could be added.

Standard treatment arm (SoC; PostOperative RT)

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, a participant must meet all of the following criteria:
• \. Women ≥18 years with histopathologically confirmed breast cancer who:
• a. require SSM/NSM for any reason (e.g. extensive disease)
• b. require postoperative radiation therapy of at least the chest wall
• c. have a wish for a breast reconstruction
• An Eastern Cooperative Oncology Group (ECOG) performance status grade ≤ 2
• Participant is able and willing to provide written informed consent, which includes compliance with and ability to undergo all study procedures, and attend the scheduled follow-up visit(s) per protocol.

You may not qualify if:

• A potential participant who meets any of the following criteria will be excluded from participation in this study:
• A previous history of breast cancer or irradiation of the chest wall for any other indication, on the other side (ipsilateral). A bilateral SSM/NSM + reconstruction (e.g. in case of a contralateral prophylactic SSM/NSM), or previous contralateral breast cancer disease/treatment, do not fall under this criterium and are thus allowed.
• Collagen synthesis disease
• Ongoing pregnancy
• Actively breastfeeding
• BMI \> 35 kg/m2
• cT4d tumour, metastatic disease or any reason making SSM/NSM not indicated

Sponsors & Collaborators

• Cancer Research Antwerp: lead
• Ziekenhuis aan de Stroom: collaborator
• Iridium netwerk: collaborator

Study Sites (6)

Universitair Ziekenhuis Antwerpen (UZA)

Edegem, Antwerpen, 2650, Belgium

RECRUITING

Ziekenhuis aan de stroom

Wilrijk, Antwerpen, 2610, Belgium

RECRUITING

AZ Klina

Brasschaat, Antwerp, 2930, Belgium

NOT YET RECRUITING

CHU Namur

Namur, Namur, 5000, Belgium

RECRUITING

Universitair Ziekenhuis Gent (UZGent)

Ghent, Oost Vlaanderen, 9000, Belgium

NOT YET RECRUITING

AZ Groeninge

Kortrijk, West Vlaanderen, 8500, Belgium

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Melanie Machiels, MD, PhD

  Iridium netwerk

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tom Quisenaerts, MD

CONTACT

+3234433759; Tom.quisenaerts@zas.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study due to the impracticalities and ethical considerations regarding blinding of both radiation therapy and (sham-)surgeries. The assessment of the photographs by an external expert panel will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter phase 3 (non-pharmacological) randomized controlled trial, with a parallel design and a 1:1 assignment ratio.

Study Record Dates

• First Submitted: December 2, 2024
• First Posted: December 18, 2024
• Study Start: February 20, 2025
• Primary Completion (Estimated): February 20, 2029
• Study Completion (Estimated): February 20, 2038
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be shared after assessment of the primary endpoint, and subsequently at an interval in accordance with the further follow-up visits.
• Access Criteria: Access to the finalised database can be requested after primary endpoint assessment. Requests will be handled on a case-by-case basis. Data will only be shared for scientific purposes, and is only permitted after ethical commission approval, and DTA signing.

Locations

BE (6)