Single-dose Preoperative Partial Breast Irradiation in Low-risk Breast Cancer Patients

Breast Cancer Clinical Trial

— ABLATIVE-2  

Official title:

Single-dose Preoperative Partial Breast Irradiation in Low-risk Breast Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05350722
• Other study ID #: NL77000.029.21
• Status: Recruiting
• Phase: N/A
• Start date: August 24, 2022
• Est. completion date: March 2035

Study information

• Verified date: September 2022
• Source: Amsterdam UMC, location VUmc
• Contact: Yasmin Civil, MD
• Phone: 020 4441484
• Email: y.civil[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 2035
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC	Amsterdam

Sponsors (2)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc	Dutch Cancer Society

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic complete response	pCR is defined as the absence of residual invasive cancer on resected breast specimen	12 months after radiotherapy
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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