Clinical trial NCT06671691: A Phase I Dose-escalation Trial of Definitive Single Dose Stereotactic Body Radiotherapy in Low-risk Breast Cancer Patients: DESERT I Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3)
SBRT
Keywords: Breast cancer
SBRT
Radiotherapy
early stage
Definitive treatment
Lead sponsor: Universitat de les Illes Balears
Sponsor class: OTHER
First posted: 2024-11-04
Enrollment: 15
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Treatment tolerance will be the basis for allowing us to progress to the next dose level.

Dose-limiting toxicity (DLT) will be defined as a G3-G4 toxicity or G2 in cases of hypo/hyperpigmentation according to the CTCAE v5.0 scale, assessing the following items: induration, ulceration, pruritus, pigmentation changes, and fatigue. If, at 3 months post-RT at the initial dose level, none of the patients present a DLT, three new patients will receive RT at the next dose level. However, if any patient in a group presents a DLT, three additional patients will be added at the same dose level. Dose escalation will continue up to 30Gy unless \>33% of patients in a single dose group experience a DLT.

If \>33% of patients at a dose level experience a DLT, the study will end, and the dose level immediately below this will be selected to design the phase II of the study.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Establish the single-fraction radiation dose (MTD)
timeFrame: 3 months
Secondary outcomes:
measure: Chronic toxicity
timeFrame: 1 year
measure: Radiological response to treatment
timeFrame: 1 year
measure: Pathological response to treatment
timeFrame: 1 year
measure: Patient-reported quality of life
timeFrame: 1 year
measure: Cosmesis after treatment
timeFrame: 1 year
measure: Tumor DNA sequencing
timeFrame: 1 year
Other outcomes:
Locations:
city: Palma
country: Spain
facility: Hospital Universitario Son Espases
state: Islas Baleares
Study officials:
affiliation: Universitat de les Illes Balears
name: Jon Gadea Quinteiro, Principal investigator
role: PRINCIPAL_INVESTIGATOR
References: