Single-dose Preoperative Partial Breast Irradiation in Low-risk Breast Cancer Patients (ABLATIVE-2)

In this ABLATIVE-2 trial, low-risk breast cancer patients will be treated with MRI-guided single dose preoperative partial breast radiotherapy to assess the rate of pathologic complete response after an interval of six to twelve months between radiotherapy and surgery. Response monitoring will be assessed using MRI and markers in blood and tumor tissue to enable prediction of pathologic response.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Single dose ablative radiotherapy

Detailed Description

Patients will receive single-dose preoperative radiotherapy followed by breast conserving surgery (BCS) at 12 months after radiotherapy, as long as follow-up MRI scans show a complete radiologic response. In case of incomplete radiologic response, BCS will be performed at 6 months after radiotherapy. BCS is performed earlier when progressive disease is found on MRI. In the follow-up period between radiotherapy and surgery, tumor response will be monitored using MRI every 3 months. After surgery, patients will be followed up until 10 years after radiotherapy treatment to assess oncological outcomes, toxicity, cosmetic outcome and quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yasmin Civil, MD; Phone Number: 020 4441484; Email: y.civil@amsterdamumc.nl
• Study Contact Backup: Name: Desirée van den Bongard, MD, PhD; Email: h.j.vandenbongard@amsterdamumc.nl

Study Locations

• Australia
  • Sydney, Australia
    • Not yet recruiting
    • GenesisCare
    • Contact: Gillian Lamoury, MD; Phone Number: +61400415836; Email: Gillian.Lamoury@health.nsw.gov.au
• Netherlands
  • Almere, Netherlands
    • Recruiting
    • Flevoziekenhuis
    • Contact: Gwen Diepenhorst, MD PhD; Phone Number: +31368688888; Email: gdiepenhorst@flevoziekenhuis.nl
  • Amstelveen, Netherlands
    • Recruiting
    • Ziekenhuis Amstelland
    • Contact: Astrid Baan, MD; Phone Number: +31207557000; Email: a.baan@zha.nl
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC
    • Contact: Yasmin Civil, MD; Phone Number: 0031 20 4441484; Email: y.civil@amsterdamumc.nl
  • Nijmegen, Netherlands
    • Recruiting
    • Radboud UMC
    • Contact: Paulien Westhoff, MD PhD; Phone Number: +31243614505; Email: Paulien.Westhoff@radboudumc.nl
  • Nijmegen, Netherlands
    • Recruiting
    • Canisius Wilhelmina Ziekenhuis
    • Contact: Dominique van Uden, MD PhD; Phone Number: +31243657657; Email: d.vanuden@cwz.nl
  • Zaandam, Netherlands
    • Recruiting
    • Zaans Medisch Centrum
    • Contact: Sandra Muller, MD PhD; Phone Number: +31756502911; Email: muller.dr.s@zaansmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• WHO performance scale ≤2.

• Females at least 50 years of age with unifocal cT1N0 breast cancer on mammography, ultrasound and MRI.

  • Patients with an indication for chemotherapy or HER2-targeted therapy according to Dutch National Oncoline Guidelines or own hospital protocols are not eligible. Patients with an indication for endocrine therapy are eligible.
  • Tumor size as assessed on MRI.

• On tumor biopsy:

  • Bloom-Richardson grade 1 or 2.
  • Non-lobular invasive histological type carcinoma.
  • LCIS or (non-extensive) DCIS is accepted.
  • ER positive tumor receptor.
  • HER2 negative tumor.
• Tumor-negative sentinel node (excluding isolated tumor cells).
• Adequate communication and understanding skills of the Dutch language.

Exclusion Criteria:

• Legal incapacity.
• BRCA1, BRCA2 or CHEK2 gene mutation.
• Distant metastasis.
• Previous history of breast cancer or DCIS.
• Other type of malignancy within 5 years before breast cancer diagnosis. Patients with adequately treated malignancy longer than 5 years before breast cancer diagnosis are eligible for inclusion.
• For adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin no specific time span to breast cancer diagnosis is required for inclusion.
• Collagen synthesis disease.
• Signs of extensive DCIS component on histological biopsy or on imaging (e.g. no extensive calcifications on mammography).
• Invasive lobular carcinoma.
• MRI absolute contraindications as defined by the Department of Radiology.
• Nodal involvement with cytological or histological confirmation.
• Indication for treatment with (neo-)adjuvant chemotherapy.
• Non-feasible dosimetric RT plan.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-operative single dose partial breast irradiation	Radiation: Single dose ablative radiotherapy; Patients will receive a single dose of 20Gy/15Gy on the gross tumor volume and clinical tumor volume respectively, in the context of pre-operative partial breast irradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response	pCR is defined as the absence of residual invasive cancer on resected breast specimen	12 months after radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiologic complete response	Radiologic complete response (rCR) is defined as complete absence of pathologic contrast enhancement in the original tumor bed and complete absence of pathologic ADC (apparent diffusion coefficient) reduction in the original tumor bed. rCR is reported according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines.	at baseline, 2 weeks, 3, 6, 9, and 12 months after radiotherapy
Treatment-related adverse events	Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria Adverse Events version 5.0	at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy
Patient quality of life	PROMs are assessed using the European Organization for Research and Treatment of Cancer core-30 quality of life questionnaire (EORTC QLQ-C30)	at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy
Breast cancer specific quality of life	PROMs are assessed using the European Organization for Research and Treatment of Cancer breast cancer-specific quality of life questionnaire (EORTC QLQ-BR23)	at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy
Patient distress	PROMs are assessed using the Hospital Anxiety and Depression Scale (HADS) questionnaire	at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy
Physician reported cosmetic outcome	Cosmetic outcome is assessed by the physician using a questionnaire	at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy
Patient reported cosmetic outcome	Cosmetic outcome is assessed by the patient using the BREAST-Q questionnaire. .	at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy
Objective cosmetic outcome	Cosmetic outcome is assessed objectively using images captured using the VECTRA XT 3D-imaging system. This three-dimensional surface-imaging system uses stereophotogrammetry to estimate x, y, z coordinates of the imaged surface. These coordinates will be used to calculate the volume-shape-symmetry measure.	at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy
Local, regional and distant relapse rates	A local recurrence is defined as disease occurrence in the ipsilateral breast. A regional recurrence is defined as nodal occurrence in the ipsilateral axilla, internal mammary, infraclavicular or supraclavicular region. A distant metastasis defined as disease occurrence in the contralateral breast or contralateral breast nodal region or another organ than breast involvement.	Day of radiotherapy till end of follow-up of 10 years
Overall survival	Overall survival will be calculated from the date of the radiotherapy treatment until the time of breast-cancer related death or breast-cancer unrelated death.	Day of radiotherapy till end of follow-up of 10 years
Radiotherapy-associated immune response markers	Immune response markers as CD3, CD4, CD8 and FOXP3 will be assessed in tumor tissue after surgery.	12 months after radiotherapy
Radiotherapy-associated biomarkers	ctDNA will be assessed in blood samples taken between radiotherapy and surgery.	at baseline, 2 weeks, 3, 6, 9, and 12 months after radiotherapy

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Dutch Cancer Society
• Investigators: Principal Investigator: Desirée van den Bongard, MD, PhD, Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2037

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 27, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: quality of life; survival; Early stage breast cancer; toxicity; Partial breast irradiation; pathologic complete response; Pre-operative radiotherapy; cosmetic outcome; neo-adjuvant radiotherapy; oncological outcomes; Low-risk breast cancer; Pre-operative single dose radiation
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: NL77000.029.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No