Ultrahypofractionated Versus Normofractionated Sequential Boost After Whole-breast Radiation Therapy in Patients Treated With Breast-conserving Surgery for Breast Cancer

NCT07590505 | Completed Phase 3

• 1 other identifier: CTO21030GZA
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

The ULTIMO trial is a monocentric, prospective, randomised controlled, open-label, phase III interventional clinical trial, with a non-inferiority design, in patients with breast cancer undergoing breast conservative treatment (BCT). After giving informed consent and verifying eligibility, data collection starts and patients will be randomized in one of the following treatment arms:

• Standard treatment arm: Breast Conserving Surgery (BCS) takes place, followed by the SoC hypofractionated Whole Breast Radiation Therapy (WBRT) and SoC normofractioned sequential boost (normSEB) of 10Gy over 5 fractions.
• Experimental treatment arm: Breast Conserving Surgery (BCS) takes place, followed by the SoC hypofractionated WBRT and experimental ultrahypofractionated sequential boost (ultSEB) of 6Gy in a single fraction. The primary objective of the ULTIMO study is to assess whether the ultSEB RT boost protocol is non-inferior to the current SoC normSEB RT boost protocol. This assessment will be based on the cosmetic outcome of the breasts, while also taking into account quality of life (QoL), the frequency and intensity of (S)AEs of interest (breast pain and fibrosis), and oncological survival.

Conditions

Breast Cancer

Keywords

breast; cancer; breastcancer; radiotherapy; radiationtherapy; radiation therapy; breast conserving surgery; whole breast radiation therapy; hypofractionated boost; neoplasm

Outcome Measures

Primary Outcomes (3)

• Cosmetic non-inferiority - BCCT.core scoring

  Operationalisation: BCCT.core is a software package for evaluating photographs of breasts after BCS. The 'Global cosmetic result' from the two frontal photos (arms up, and arms down) will be averaged and then used as the individual value of this measure. The results are scored on a 4-point Likert scale, coded as 0-3. Analysis metric: The change from baseline at 1 and 3YFU will be used. Negative values will be transformed to '1' to signal an inferiority event, positive or values of zero will be transformed to '0' to signal non-inferiority. For comparisons and estimands, please refer to the SAP. Method of aggregation: The results will be reported as a contingency table reporting both frequencies and proportions of non-inferior and inferior results in each treatment arm. Time point(s): A baseline assessment is performed during the screening visit, followed by repeated measurements during the 1 and 3YFU (primary endpoint) visits.

  From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.

• Cosmetic outcome - Expert panel, AIS-TAS

  Operationalisation: The AIS is a tool for scoring breast cosmesis based on standardized photos. It comprises of 5 items, each comprising of a 5 point Likert-scale, coded as 1 to 5. The score is given based on the group of photos taken at a single time point. The scores of all items are summed to produce the TAS, which consequently ranges from 5 to 25. The AIS is used in an expert panel setting, where all scores, from each assessor are averaged per item. A higher scores represents a more favourable cosmetic outcome. Analysis metric: AIS-TAS absolute values will be used for analysis. Method of aggregation: The mean, median, SD and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit, followed by repeated measurements during the 1 and 3YFU (primary endpoint) visits.

  From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.

• Cosmetic outcome - Expert panel, AIS-Symmetry

  Operationalisation: The AIS is a tool for scoring breast cosmesis based on standardized photographs. It comprises of 5 items, each comprising of a 5 point Likert-scale, coded as 1 to 5. The score is given based on the group of photos taken at a single time point. The AIS is used in an expert panel setting, where all scores, from each assessor are averaged per item. A higher scores represents a more favourable cosmetic outcome. Analysis metric: AIS-Symmetry score absolute values will be used for analysis. Method of aggregation: The mean, median, SD and IQR will be reported. For comparisons and estimands, please refer to the SAP. Time point(s): A baseline assessment is performed during the screening visit, followed by repeated measurements during the 1 and 3YFU (primary endpoint) visits.

  From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.

Secondary Outcomes (14)

• Cosmetic outcome - Physician scoring

  From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.

• Cosmetic outcome - Patient reported (PROM)

  From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.

• Quality of life - EORTC QLQ C30 v3 - Global health status/QoL

  From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.

• Quality of life - EORTC QLQ C30 v3 -Functional scales

  From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.

• Quality of life - EORTC QLQ C30 v3 -Symptom scales

  From enrollment to the end of follow-up at 3 years of follow-up, counting from the last study visit.

Study Arms (2)

Standard treatment arm (SoC; Normofractionated boost RT)

ACTIVE COMPARATOR

In the control arm, the boost of the radiation therapy will be delivered according to the standard of care fractionation and dosage scheme. This consists of 5 fractions of 2Gy each, adding up to a total dose of 10Gy. All other treatments are not considered to be study-specific and are performed according to the standard of care treatment for breast cancer.

Radiation: Standard of Care (SOC) - Normofractionated Sequential Boost Radiation Therapy

Experimental treatment arm (Hypofractionated boost RT)

EXPERIMENTAL

In the experimental arm, the boost of the radiation therapy is delivered in a ultrahypofractionated scheme. This consists of a single fraction of 6Gy. All other treatments are not considered to be study-specific and are performed according to the standard of care treatment for breast cancer.

Radiation: Experimental - UltraHypofractionated Sequential Boost Radiation Therapy

Interventions

Standard of Care (SOC) - Normofractionated Sequential Boost Radiation Therapy RADIATION

Standard of care fractionation and dosage scheme of the sequential radiation therapy boost. This consists of 5 fractions of 2Gy each, adding up to a total dose of 10Gy.

Also known as: normSEB

Standard treatment arm (SoC; Normofractionated boost RT)

Experimental - UltraHypofractionated Sequential Boost Radiation Therapy RADIATION

The radiation therapy sequential boost is delivered in a ultrahypofractionated scheme. This consists of a single fraction of 6Gy.

Also known as: ultSEB

Experimental treatment arm (Hypofractionated boost RT)

Eligibility Criteria

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

You may qualify if:

• Breast cancer patients referred for WBRT + boost to the lumpectomy cavity
• Patients ≥18y
• Karnofsky Performance Score \>70%, or ECOG \<2
• Life expectancy of more than 5 years
• Invasive tumour free resection margins, defined as R0 resection on the pathology report
• Written informed consent

You may not qualify if:

• Previous contralateral breast cancer
• Previous RT of the same breast or thorax.
• Metastatic disease (M1)

Sponsors & Collaborators

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

Study Sites (1)

Ziekenhuis aan de stroom

Antwerp, Antwerpen, 2610, Belgium

Location

Related Links

• This link refers to the video abstract of the interim analysis presented at the San-Antonio Breast Cancer meeting in 2024.

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Melanie Machiels, MD, PhD

  Iridium netwerk

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The ULTIMO trial is a prospective, interventional, randomised (RCT), phase 3, open label clinical trial.

Study Record Dates

• First Submitted: May 6, 2026
• First Posted: May 15, 2026
• Study Start: March 29, 2022
• Primary Completion: November 28, 2025
• Study Completion: March 25, 2026
• Last Updated: May 15, 2026

Record last verified: 2026-05

Locations

BE (1)