CRYoablation for Small Tumors As Local Treatment - SIX Trial

Phase 3

Not yet recruiting

• Conditions: Breast Cancer; Breast Neoplasm

• Registration Number: NCT06839001
• Lead Sponsor: Hospital do Coracao

Brief Summary

To demonstrate the non-inferiority of cryoablation compared to breast surgery for the local treatment of early-stage breast cancer and to conduct a cost-minimization analysis comparing direct costs between treatments.

Detailed Description

This study compares cryoablation with breast surgery for the treatment of early-stage breast cancer (T1N0M0), evaluating locoregional recurrence, cost-minimization, and disease-free survival.

The primary objective is to demonstrate the non-inferiority of cryoablation compared to breast surgery for local treatment of early-stage breast cancer over five years, as well as to perform a cost-minimization analysis to compare the direct costs of both treatments over one year.

The secondary objectives include assessing locoregional recurrence at one year, evaluating disease-free survival and overall survival over five years, analyzing circulating tumor cells (CTCs) as prognostic factors and for monitoring cryoablation at baseline (study inclusion), six months, and twelve months, measuring patient satisfaction one year after randomization using the Breast-Q questionnaire, and assessing quality of life using the EQ-5D questionnaire.

Cryoablation is a nonsurgical, minimally invasive technique that destroys tumor tissue through cyclic freezing and thawing using cryoprobes. This process induces cellular death without requiring hospitalization, allowing for faster recovery.

Additionally, the study incorporates a de-escalated and personalized approach to breast cancer treatment by omitting sentinel lymph node biopsy, integrating ultrahypofractionated radiotherapy, and utilizing liquid biopsy.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-16
• Study First Submitted QC: 2025-02-16
• Last Update Submitted: 2025-02-16
• Study First Posted: 2025-02-21
• Last Update Posted: 2025-02-21
• Study Start: 2025-03-01
• Primary Completion: 2027-03-01
• Study Completion: 2030-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 750

Inclusion Criteria

• Unifocal primary invasive breast carcinoma
• Tumor size ≤ 2.0 cm (T1)
• Complete pathological report (including results for ER, PR, HER2, Ki-67, and FISH report for the ERBB2 gene, if necessary)
• Lesion visible on ultrasound
• Surgical treatment would be the first option, regardless of immunohistochemistry results

Exclusion Criteria

• Multifocal or multicentric invasive breast carcinoma
• Ductal carcinoma in situ
• Breast cancer with skin involvement
• Clinically positive axilla (N1, N2 or N3)
• Distance from lesion and skin less than 5 mm
• Prior neoadjuvant systemic therapy for breast cancer
• Distant metastasis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Locoregional recurrence (LRR)	5 years	LRR was defined as recurrence in the ipsilateral breast or chest wall, as well as in the ipsilateral axillary, supraclavicular/infraclavicular region, or internal mammary lymph nodes detected during follow-up, regardless of whether distant metastasis occurred before, after, or simultaneously.
Cost-minimization	1 year	A cost-minimization analysis is an economic technique used to compare the costs of different interventions or treatments that produce equivalent outcomes in terms of efficacy and clinical effects. In other words, this analysis is applied when treatments are assumed to have the same clinical effectiveness, and the goal is to determine which one has the lowest cost. It is a type of cost-effectiveness analysis that compares only the costs of two or more technologies, as the health effects resulting from the compared technologies are considered similar. Clinical outcomes will not be taken into account. We will calculate the costs by collecting data on both direct and indirect expenses associated with the treatments. Direct costs will include procedure-related expenses such as equipment, supplies, medical fees, associated tests and consultations, hospitalization costs if applicable, and medication use. Indirect costs, if a societal perspective is considered, will include factors such as ti

Secondary Outcome Measures

Name	Time	Method
Locoregional recurrence (LRR)	1 year	LRR was defined as recurrence in the ipsilateral breast or chest wall, as well as in the ipsilateral axillary, supraclavicular/infraclavicular region, or internal mammary lymph nodes detected during follow-up, regardless of whether distant metastasis occurred before, after, or simultaneously.
Patient satisfaction	1 month	Patient satisfaction will be assessed using the Breast-Q questionnaire, a validated tool designed to measure patient-reported outcomes related to breast surgery and treatment.
Disease-free survival (DFS)	5 years	DFS is defined as the time from procedure to time of ipsilateral recurrence, contralateral recurrence, regional recurrence or distant metastasis, or date of last follow-up if none of the recurrence events occur.
Overall Survival (OS)	5 years	OS is defined as the time from the date of first dose to the date of death due to any cause.
Circulating tumor cells (CTCs)	1 year	CTCs are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood. Blood samples will be collected from participants included in the study at the time of the procedure, at 6 months, and at 1 year. A total of 10 mL of blood will be drawn via peripheral venipuncture into EDTA tubes (BD Vacutainer®), which will be maintained under homogenization for up to 6 hours at room temperature until filtration is performed (ISET®; Rarecells Diagnostics, Paris, France). CTCs will be identified through cytopathological analysis. After filtration, membranes washed with PBS and air-dried will be stored at -20°C until analysis. Blood samples for CTC research will preferably be sent within 48 hours and no later than 72 hours to the coordinating center.
EQ-5D questionnaire	1 year	Quality of life will be assessed using the EQ-5D questionnaire. The EQ-VAS (Visual Analogue Scale) thermometer is a component of the EQ-5D, a standardized instrument for measuring health-related quality of life. In the EQ-VAS, patients evaluate their own health status at a given moment using a numerical scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

Trial Locations

Locations (1)

Research Institute - Hospital do Coracao; 🇧🇷 Sao Paulo, SP, Brazil