Clinical trial NCT06640881: Preoperative Partial Breast Reirradiation and Repeat Breast-conserving Surgery in Patients With Recurrent Breast Cancer: the REPEAT Trial
Official title: Preoperative Partial Breast Reirradiation and Repeat Breast-conserving Surgery in Patients With Recurrent Breast Cancer: the REPEAT Trial - a Study Protocol
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Recurrent Breast Carcinoma
Ipsilateral Recurrence
Keywords: single-dose preoperative radiotherapy
pathologic response
radiologic response
cosmetic outcome
partial breast irradiation
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2024-10-15
Enrollment: 25
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Over the past decades, interest in second breast-conserving therapy (BCT) has increased due to, among others, advancements in radiotherapy techniques. Preoperative partial breast irradiation (PBI) is an experimental treatment for patients with low-risk primary breast cancer. This approach can downstage the tumor, and may possibly reduce toxicity and improve cosmetic outcomes compared to postoperative radiotherapy. This study aims to evaluate the feasibility of single-dose preoperative PBI and second breast-conserving surgery (BCS) for patients with an ipsilateral recurrent breast event (IRBE) after previous BCT.

The REPEAT trial is a multicenter, prospective, single-arm trial investigating ablative single-dose preoperative PBI in patients with an IRBE. Eligible patients are ≥ 50 years, have a unifocal non-lobular invasive breast cancer ≤ 2 cm, Bloom-Richardson grade 1 or 2, estrogen receptor-positive, HER2-negative and clinically negative axillary lymph nodes. The study plans to enroll 25 patients. Radiotherapy planning will involve the use of CT and MRI in the treatment position. Single-dose PBI of 20 Gy to the tumor and 15 Gy to the surrounding 2 cm of breast tissue will be delivered using a conventional or MR-guided linear accelerator. Tumor response will be monitored preoperatively using MRI and liquid biopsies to identify biomarkers for evaluating radiosensitivity. BCS will be performed 3 weeks post-PBI. The primary endpoint is the incidence of grade 2 or higher treatment-associated acute toxicity within 90 days. Secondary endpoints include the evaluation of acute (grade 1) and late toxicity, radiologic and pathologic response, mastectomy rate, patient-reported outcomes, cosmetic outcome, local, regional and distant recurrence rates, survival outcome, and biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 5 years after PBI.

This trial will evaluate the feasibility of single-dose preoperative PBI and BCS for patients with IRBE. This treatment approach is expected to minimize the irradiated volume, reduce toxicity, and improve cosmetic outcomes compared to postoperative PBI after second BCS. Identifying biomarkers for radiosensitivity will help in selection patients and tailoring treatment.


Eligibility criteria: Inclusion Criteria:

* Female ≥ 50 years with an ipsilateral invasive recurrent breast cancer event after previous breast-conserving surgery and postoperative whole breast irradiation
* World Health Organization performance status 0-2
* Tumor size ≤ 2 cm and unifocal on MRI
* Tumor histology as assessed on biopsy:

Bloom-Richardson grade 1 or 2 Non-lobular invasive histological type carcinoma Estrogen receptor positive HER2 receptor negative No lymphovascular invasion

* No extensive DCIS (outside tumor size of 2 cm) on mammography or tumor biopsy, including non-mass enhancement on MRI
* Clinical node negative on 18-F FDG PET-CT, ultrasound and MRI
* No distant metastasis
* No or mild late toxicity (no grade 2 or higher) from previous breast-conserving therapy
* Adequate understanding of the Dutch language

Exclusion Criteria:

* Ipsilateral invasive breast cancer event less than two years after first breast-conserving therapy for breast cancer
* Other malignancy within 5 years before ipsilateral breast recurrence diagnosis. For carcinoma in situ no specific time span to ipsilateral breast recurrence diagnosis is required for inclusion
* Known breast cancer mutation gene carrier
* Collagen synthesis disease (e.g. osteogenesis imperfect, Ehlers-Danlos syndrome, systemic sclerosis)
* Previous ipsilateral mastectomy
* Invasive lobular carcinoma, DCIS without invasive cancer
* MRI absolute contraindications
* Indication for treatment with neoadjuvant chemotherapy
* Legal incapacity

Primary outcomes:
measure: Acute toxicity
timeFrame: 90 days
Secondary outcomes:
measure: Toxicity
timeFrame: 3,6,12 weeks and 1,2,3,4,5 years
measure: response
timeFrame: 3,6,12 weeks and 1,2,3,4,5 years
measure: PROMS
timeFrame: 3,6,12 weeks and 1,2,3,4,5 years
measure: cosmetic results
timeFrame: 3,6,12 weeks and 1,2,3,4,5 years
measure: oncological outcomes
timeFrame: 1,2,3,4,5 years
measure: immune response
timeFrame: 3,6,12 weeks and 1,2,3,4,5 years
measure: patient comfort during RT treatment delivery
timeFrame: during RT treatment
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC / VU Medical Centre
Study officials:
affiliation: AUMC
name: Desiree HJG van den Bongard, dr
role: PRINCIPAL_INVESTIGATOR
References: