A Phase I Dose-escalation Trial of Definitive Single Dose Stereotactic Body Radiotherapy in Low-risk Breast Cancer Patients: DESERT I Trial

Phase 1

• Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3); SBRT

• Registration Number: NCT06671691
• Lead Sponsor: Universitat de les Illes Balears

Brief Summary

Radiotherapy (RT) is a fundamental pillar in the fight against cancer. In the case of breast cancer, RT has traditionally been applied as an adjuvant treatment following surgery. However, in recent years, there has been research into the potential benefit of administering RT prior to surgery in a neoadjuvant manner. Given that these studies have shown promising results, it is logical to think that certain patients could benefit from exclusive RT treatment, thereby avoiding surgery and its possible sequelae. This study is a phase I dose-escalation clinical trial with sequential assignment, open-label, in which five different doses (20Gy, 23Gy, 26Gy, 28Gy, and 30Gy) will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique.

The aim of the study is to determine the maximum tolerated dose (MTD) based on acute toxicity, which will allow us to proceed with a phase II clinical trial to confirm efficacy and assess the late toxicity of the treatment. Secondary objectives include assessing the pathological response via core needle biopsy (CNB), radiological response, quality of life, and cosmesis. Additionally, molecular studies will be conducted on tissue and through liquid biopsy; pre- and post-treatment, we aim to identify mutations and predictors of response.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-09-27
• Status Verified: 2024-10
• Study First Submitted: 2024-10-28
• Study First Submitted QC: 2024-10-31
• Last Update Submitted: 2024-10-31
• Study First Posted: 2024-11-04
• Last Update Posted: 2024-11-04
• Primary Completion: 2025-09
• Study Completion: 2027-09

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: Female
• Target Recruitment: 15

Inclusion Criteria

• Over 18 years of age
• Female gender
• ECOG score 0-2
• Positive biopsy for invasive non-lobular breast tumor histology
• Tumor < 3 cm in diameter as measured by MRI or contrast mammography
• Tumor located ≥ 0.5 cm from the skin or rib cage, clinically or radiologically
• Positive estrogen and/or progesterone receptors
• HER2 negative
• No lymphovascular invasion in the biopsy
• Tumor must be clinically and radiologically N0 (no lymph node involvement). If a suspicious lymph node is seen, it must be biopsied and show a negative result
• Patient weight below 220 kg (weight limit for the treatment table)
• Ability to tolerate the supine position for 20 minutes during treatment
• Able to undergo MRI and/or contrast mammography
• Not pregnant; women of childbearing potential will undergo a pregnancy test to rule this out
• Contraindication to or refusal of surgical treatment, which must be explicitly documented in the medical record.

Exclusion Criteria

• Under 18 years of age
• Male gender
• ECOG score 3-4
• Positive biopsy for invasive lobular carcinoma or ductal carcinoma in situ
• Tumor ≥ 3 cm in diameter as measured by MRI
• Tumor located < 0.5 cm from the skin or rib cage, clinically or radiologically
• Negative estrogen and progesterone receptors
• HER2 positive
• Presence of lymphovascular invasion in the biopsy
• Positive BRCA mutation
• Multicentric tumor
• Tumor with positive axillary lymph nodes
• Patients with metastatic disease
• History of previous breast cancer in the same breast
• Previous thoracic radiotherapy
• Pregnant or actively breastfeeding
• Unable to undergo MRI or contrast mammography
• Unable to tolerate the supine position
• Patient with breast implants
• Patients with pacemakers
• Scleroderma, lupus, or other connective tissue diseases with active flares
• Inability to understand and sign the informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Establish the single-fraction radiation dose (MTD)	3 months	To establish the single-fraction SBRT radiation dose (MTD) that causes an incidence of dose-limiting toxicities (DLTs) lower than 33%

Secondary Outcome Measures

Name	Time	Method
Chronic toxicity	1 year	Assessed at 6 and 12 months post-treatment using CTCAE v5.0 criteria for skin, fatigue, and breast.
Radiological response to treatment	1 year	Measured with MRI or contrast mammography 12 months post-RT using RECIST criteria.
Pathological response to treatment	1 year	Between 1 and 3 core needle biopsies (CNB) will be performed, guided by ultrasound on the treated lesion at 6 and 12 months post-RT to establish the rate of residual tumor cells scored by pathology review of H\&E slides.
Patient-reported quality of life	1 year	Measured using the EORTC QLQ-C30 questionnaires before RT and at 3 and 12 months post-treatment.; EORTC QLQ-C30- scale goes from 1/not at all to 4/very much. There is additionally a rate of overall health and quality of life that is a scale from 1 to 7.
Cosmesis after treatment	1 year	Measured using the Modified Harvard-Harris Cosmetic Scale (MHHCS) at 1, 3, 6, and 12 months post-treatment. Photographs of the breasts will be taken before treatment and at each follow-up visit, to be evaluated later using an external validation system.; The MHCCS scale compares baseline images with those obtained post-treatment, allowing the assessment of cosmesis as follows: Poor, fair, good or excellent.
Tumor DNA sequencing	1 year	Tumor biopsies will be taken before and at 6 and 12 months post-treatment. Next Generation Sequencing (NGS) will be performed to characterize radiation-induced changes in tumor DNA.

Trial Locations

Locations (1)

Hospital Universitario Son Espases; 🇪🇸 Palma, Islas Baleares, Spain