CRYoablation for Small Tumors As Local Treatment - SIX Trial (CRYSTAL - SIX)

Hospital do Coracao

Status and phase: Enrolling; Phase 3

Conditions: Breast Cancer; Breast Neoplasm

Treatments: Procedure: Breast Surgery (Lumpectomy or Mastectomy); Procedure: cryoablation

Study type: Interventional

Funder types: Other

Identifiers

NCT06839001

7.241.846

Details and patient eligibility

About

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.

Full 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.

Enrollment: 750 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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750 participants in 2 patient groups

Cryoablation

Experimental group

Description:

Patients will be treated with cryoablation using a Cryoprobe under real-time ultrasound guidance and local anesthesia. The cryoablation procedure consists of a freezing phase followed by passive thawing, ending with a second freezing cycle. It is recommended to use 6 minutes of freezing and 4 minutes of thawing with Cryocare, and 10 minutes of freezing and 10 minutes of thawing with ProSense IceCure®. The freeze-thaw-freeze times may be adjusted at the physician's discretion depending on tumor size. Patients will be treated with cryoablation (Day 1) using a single Cryoprobe, followed by adjuvant treatment. In cases where radiotherapy is indicated, the preferred regimen will be the 5-fraction schedule. If the 5-fraction regimen is not feasible, the radiation oncologist will be allowed to adjust the fractionation as needed. Patients assigned to the cryoablation group will not undergo axillary surgery, as axillary surgery will be omitted.

Breast Surgery (Lumpectomy or Mastectomy)

Active Comparator group

Description:

Surgery will be performed under general anesthesia according to standard operative procedures at the hospital of origin. Surgery may be performed as either a lumpectomy or a mastectomy, along with a sentinel lymph node biopsy. After surgery, patients will undergo adjuvant treatment as indicated. If radiotherapy is required, the preferred regimen will be the 5-fraction schedule. If the 5-fraction regimen is not feasible, the radiation oncologist will be allowed to adjust the fractionation as needed.

Treatment:

Procedure: Breast Surgery (Lumpectomy or Mastectomy)