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

Phase I Dose-Escalation Clinical Trial of Definitive Single Dose Stereotactic Body Radiotherapy in Patients with Low-risk Hormone Receptor-positive and Her2-negative Breast Cancer Not Suitable or Who Refuse Surgery: DESERT I Trial

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: SBRT; Breast Cancer Early Stage Breast Cancer (Stage 1-3)
• Intervention / Treatment: Radiation: SBRT level I; Radiation: SBRT level II; Radiation: SBRT level III; Radiation: SBRT level IV; Radiation: SBRT level V

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Islas Baleares
    • Palma, Islas Baleares, Spain, 07120
      • Hospital Universitario Son Espases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SBRT level I: 20Gy; 20Gy in 1 fraction will be delivered to the tumor	Radiation: SBRT level I; 20Gy in 1 fraction will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique
Experimental: SBRT level II: 23Gy; 23Gy in 1 fraction will be delivered to the tumor	Radiation: SBRT level II; 23Gy in 1 fraction will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique
Experimental: SBRT level III: 26Gy; 26Gy in 1 fraction will be delivered to the tumor	Radiation: SBRT level III; 26Gy in 1 fraction will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique
Experimental: SBRT level IV: 28Gy; 28Gy in 1 fraction will be delivered to the tumor	Radiation: SBRT level IV; 28Gy in 1 fraction will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique
Experimental: SBRT level V: 30Gy; 30Gy in 1 fraction will be delivered to the tumor	Radiation: SBRT level V; 30Gy in 1 fraction will be tested on the tumor using stereotactic body radiotherapy (SBRT) technique

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic toxicity	Assessed at 6 and 12 months post-treatment using CTCAE v5.0 criteria for skin, fatigue, and breast.	1 year
Radiological response to treatment	Measured with MRI or contrast mammography 12 months post-RT using RECIST criteria.	1 year
Pathological response to treatment	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.	1 year
Patient-reported quality of life	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.	1 year
Cosmesis after treatment	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.	1 year
Tumor DNA sequencing	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.	1 year

Collaborators and Investigators

• Sponsor: Universitat de les Illes Balears
• Investigators: Principal Investigator: Jon Gadea Quinteiro, Principal investigator, Universitat de les Illes Balears

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: October 28, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Estimated): November 4, 2024

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Breast cancer; Radiotherapy; SBRT; early stage; Definitive treatment
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: IB 5560/24 PI

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