Preoperative Radiation Therapy and Immediate Breast Reconstruction

NCT ID: NCT06739655

Last Updated: 2026-02-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-20
• Study Completion Date: 2038-02-20

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.

Detailed Description

The PRADAIIBE study is a multicentric phase III randomized controlled trial, investigating the effects of radiation therapy timing on breast reconstruction results in breast cancer patients.

This study will recruit adult female breast cancer patients from the Belgian population, who have an indication for mastectomy, Post-Mastectomy Radiation Therapy (PMRT), and also have a wish for breast reconstruction.

After informed consent is signed, patients will be screened, and included in the study if all eligibility criteria are met. If they are not eligible for participation or choose to withdraw after the ICF was signed, they will be registered as a 'screen failure'.

After study inclusion, baseline assessments take place, this includes two questionnaires, one focussed on patient's satisfaction with their own breasts (BREAST-Q v2, BQ-score), the other one focussed on their quality of life perception (EQ-5D-5L VAS-score and Index-score). Next, four photographs of the exposed breast area will be taken. These photographs will later be assessed by an expert panel (AIS-TAS).

Eligible participants are randomized using the central eCRF randomization tool (Castor EDC). Randomisation is stratified on study site and a variable block size will be used. Resulting in random assignment to one of the following treatment arms:

• Control (SoC) treatment arm: Mastectomy followed by PMRT and delayed (or immediate) breast reconstruction.
• Experimental treatment arm: preoperative radiation therapy (preop-RT) followed by mastectomy and immediate breast reconstruction.

Those assigned to the control group will follow the standard of care (SoC) treatment consisting of oncological surgery (within 6 weeks of randomisation or end of preop chemotherapy) followed by radiation therapy (PMRT) within 6-12 weeks. The breast reconstruction surgery will take place either at the same time (e.g. tissue expander implantation) as the oncological surgery, or at a delayed moment (usually a 6-12 months delay).

Patients assigned to the intervention group will receive preop-RT (within 6 weeks of randomisation or end of preop chemotherapy), and after an interval of 2-6 weeks mastectomy combined with immediate breast reconstruction will be performed. The radiation therapy will be administered according to the same principles as PMRT/Whole Breast Radiation Therapy (WBRT). This change to preoperative timing of the radiation therapy allows for immediate breast reconstruction without irradiation of the reconstructed breast.

In the unexpected event of tumour downstaging due to preoperative treatment, changing the indication from mastectomy to breast conserving surgery (BCS), while the patient has already been included, it is allowed within the study protocol to perform BCS. In this case the patient should receive the treatment and surgery which is in their best interest. The same follow-up will be provided. In statistical analysis results from such patients will be handled according to the inter-current events (ICE) strategies defined in the SAP. However, such downstaging is not expected from preop-RT at such a short treatment interval of 2-6 weeks.

Systemic therapy will be administered per standard of care, according to the discretion of the treating medical oncologist. Systemic therapy details will be registered in the eCRF, but it is not considered as part of the study treatments, and will not be manipulated within this trial.

After the treatment period is finished (last study treatment) follow-up will take place at 3 months, 1 year, 2 years, 5 years and 10 years. In the control group, patients undergoing delayed breast reconstruction will be invited to an intermediate follow up visit (IMFU) visit at 3 months after conclusion of radiation therapy. The reason for this IMFU visit is to capture the outcomes of interest in the interval between mastectomy and breast reconstruction, as well as provide continued study follow-up during this long treatment interval of +/- 6-12 months.

During each follow-up visit the BREAST-Q and EQ-5D-5L questionnaires will be assessed, photographs will be taken and evaluated at a later (expert panel using the AIS-tool), adverse events will be elicited, pathologic response assessed, treatment milestones are recorded (treatment duration) and oncological recurrence is assessed from the +1 year visit onwards according to the events and outcomes described in the DATECAN 2015 initiative.

Conditions

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

Study Design

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

Study Groups

Standard treatment arm (SoC; PostOperative RT)

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.]

Group Type: ACTIVE_COMPARATOR

Postoperative radiotherapy

Intervention Type: RADIATION

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

Immediate or delayed breast reconstruction

Intervention Type: 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.

Experimental treatment arm (PreOperative RT)

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.]

Group Type: EXPERIMENTAL

Preoperative radiotherapy

Intervention Type: 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.

Immediate breast reconstruction

Intervention Type: 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.

Interventions

Preoperative radiotherapy

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.

Intervention Type: RADIATION

Postoperative radiotherapy

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

Intervention Type: RADIATION

Immediate breast reconstruction

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.

Intervention Type: PROCEDURE

Immediate or delayed breast reconstruction

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.

Intervention Type: PROCEDURE

Other Intervention Names

Preop-RT; Neoadjuvant radiation therapy; NART; Postop-RT; Postmastectomy Radiation Therapy; PMRT; Adjuvant Radiation Therapy; ART; IBR

Eligibility Criteria

Inclusion Criteria

In order to be eligible to participate in this study, a participant must meet all of the following criteria:

1. Women ≥18 years with histopathologically confirmed breast cancer who:

1.a. require SSM/NSM for any reason (e.g. extensive disease)

1.b. require postoperative radiation therapy of at least the chest wall

1. c. have a wish for a breast reconstruction

2. An Eastern Cooperative Oncology Group (ECOG) performance status grade ≤ 2

3. 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.

Exclusion Criteria

A potential participant who meets any of the following criteria will be excluded from participation in this study:

1. 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.

2. Collagen synthesis disease

3. Ongoing pregnancy

4. Actively breastfeeding

5. Smoking at time of inclusion (a history of smoking is allowed but needs to be registered in the eCRF). No interval between smoking cessation and study inclusion is defined, but the reconstructive surgeon needs to be willing to operate the patient using autologous tissue transfer. This generally translates to a smoking cessation of >3months preoperatively.

6. BMI > 35 kg/m2

7. cT4d tumour, metastatic disease or any reason making SSM/NSM not indicated

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

Sponsors

Ziekenhuis aan de Stroom

OTHER

Sponsor Role: collaborator

Iridium netwerk

UNKNOWN

Sponsor Role: collaborator

Cancer Research Antwerp

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melanie Machiels, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Iridium netwerk

Locations

Universitair Ziekenhuis Antwerpen (UZA)

Edegem, Antwerpen, Belgium

Site Status: RECRUITING

Ziekenhuis aan de stroom

Wilrijk, Antwerpen, Belgium

Site Status: RECRUITING

AZ Klina

Brasschaat, Antwerp, Belgium

Site Status: NOT_YET_RECRUITING

CHU Namur

Namur, Namur, Belgium

Site Status: RECRUITING

Universitair Ziekenhuis Gent (UZGent)

Ghent, Oost Vlaanderen, Belgium

Site Status: NOT_YET_RECRUITING

AZ Groeninge

Kortrijk, West Vlaanderen, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Tom Quisenaerts, MD

Role: CONTACT

Tom.quisenaerts@zas.be

+3234433759 ext. +32

Facility Contacts

Isabelle Nietvelt

Role: primary

isabelle.nietvelt@uza.be

+32 3 821 30 00 ext. +32

Tom Quisenaerts, MD

Role: primary

Tom.quisenaerts@zas.be

+3234433759 ext. +32

Research AZ Klina

Role: primary

datanurse.onco@klina.be

Caroline Yague Sanz

Role: primary

caroline.yaguesanz@chuuclnamur.uclouvain.be

+32 81 72 04 11 ext. +32

Jessie De Kinder

Role: primary

jessie.dekinder@uzgent.be

+329 332 32 78 ext. +32

Inge Meyer

Role: primary

inge.meyer@azgroeninge.be

+3256 63 39 03 ext. +32

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CTO23023GZA

Identifier Type: -

Identifier Source: org_study_id