Breast CancerPhase 3CRYSTAL - SIXNCT06839001
CRYoablation for Small Tumors As Local Treatment - SIX Trial
A Phase 3 study testing cryoablation and Breast Surgery (Lumpectomy or Mastectomy) in people with Breast Cancer and Breast Neoplasm, run by Hospital do Coracao at 2 sites in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Breast Neoplasm
- What is being tested?
- cryoablation and Breast Surgery (Lumpectomy or Mastectomy)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 750 participants
- Where
- 2 sitesBrazil
- Study dates
- 1 Mar 2025to 1 Mar 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil2 sites, 2 recruiting
- Not yet recruiting
Research Institute - Hospital do Coracao
São Paulo, São Paulo, 04004-030
Vanessa Monteiro Sanvido, PhD, +55113053-6611, dravanessasanvido@gmail.com
Vanessa Monteiro Sanvido, PhD
- Recruiting
Research Institute - Hospital do Coracao
São Paulo, São Paulo, 04041-004
Vanessa Monteiro Sanvido, PhD, 11994200778, vanessasanvido@gmail.com
About this study
Official title: Cryoablation Versus Breast Surgery in the Local Treatment of Early-Stage Breast Cancer - Six Trial
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.
Read the 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.
- Conditions
- Breast Cancer, Breast Neoplasm
- Being tested
- cryoablation, Breast Surgery (Lumpectomy or Mastectomy)
- Keywords
- Breast Cancer, Minimally Invasive Surgical Procedures, Cryoablation, Locoregional Recurrence, Cost-Minimization Analysis
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cryoablationProcedure or surgery
Two devices can be used to perform cryoablation: Cryocare® and ProSense IceCure®:
- Cryocare® - This procedure utilizes two types of gases: argon gas for freezing and helium gas for thawing.
- ProSense IceCure® - This procedure uses extremely low temperatures generated by liquid nitrogen (LN2) to freeze and destroy the target tissue, without the need for an additional gas.
Breast Surgery (Lumpectomy or Mastectomy)Procedure or surgery
Surgery can be performed as lumpectomy or mastectomy and axillary surgery, preferably sentinel lymph node biopsy.
| Study group | Role | What they receive |
|---|---|---|
| Cryoablation | Experimental | 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 | 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. Receives: Procedure: Breast Surgery (Lumpectomy or Mastectomy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Locoregional recurrence (LRR)
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.
Measured: 5 years
Cost-minimization
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
Measured: 1 year
Secondary outcomes (6)
Locoregional recurrence (LRR)
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.
Measured: 1 year
Disease-free survival (DFS)
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.
Measured: 5 years
Overall Survival (OS)
OS is defined as the time from the date of first dose to the date of death due to any cause.
Measured: 5 years
Circulating tumor cells (CTCs)
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.
Measured: 1 year
Patient satisfaction
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.
Measured: 1 month
EQ-5D questionnaire
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2025
- Study start1 Mar 2025
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The initial 750 participants will be randomized in a 1:1 manner to either cryoablation or breast surgery. This is a Phase 3 randomized trial evaluating the efficacy and safety of cryoablation compared to breast surgery for early-stage breast cancer. Although the intervention does not involve drugs or biologics, it meets the criteria of a Phase 3 trial as a confirmatory study of an interventional procedure.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 750 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital do Coracao
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vanessa Monteiro Sanvido, Hospital do Coracao
- Investigators
- Vanessa Monteiro Sanvido, PhD, Principal investigator, Research Institute - Hospital do CoracaoAfonso Celso Pinto Nazário, PhD, Principal investigator, Research Institute - Hospital do CoracaoAlexandre Biasi Cavalcante, PhD, Study director, Research Institute - Hospital do Coracao
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06839001
- Sponsor's protocol ID
- 7.241.846
- Acronym
- CRYSTAL - SIX
- Status last verified
- Mar 2025
- First submitted
- 16 Feb 2025
- Last updated
- 26 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cryoablation Versus Breast Surgery in the Local Treatment of Early-Stage Breast Cancer - Six Trial
- ClinicalTrials.gov ID
- NCT06839001
- Acronym / sponsor ID
- CRYSTAL - SIX / 7.241.846
- Conditions
- Breast Cancer, Breast Neoplasm
- Keywords
- Breast Cancer, Minimally Invasive Surgical Procedures, Cryoablation, Locoregional Recurrence, Cost-Minimization Analysis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 750 participants (estimated)
- Lead sponsor
- Hospital do CoracaoUniversity, hospital or other
- Study start
- 1 Mar 2025 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Mar 2030 (estimated)
- First posted
- 21 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- The initial 750 participants will be randomized in a 1:1 manner to either cryoablation or breast surgery. This is a Phase 3 randomized trial evaluating the efficacy and safety of cryoablation compared to breast surgery for early-stage breast cancer. Although the intervention does not involve drugs or biologics, it meets the criteria of a Phase 3 trial as a confirmatory study of an interventional procedure.
| Arm | Type | Receives |
|---|---|---|
| Cryoablation | Experimental | –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 | Procedure: Breast Surgery (Lumpectomy or Mastectomy)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cryoablationTwo devices can be used to perform cryoablation: Cryocare® and ProSense IceCure®: * Cryocare® - This procedure utilizes two types of gases: argon gas for freezing and helium gas for thawing. * ProSense IceCure® - This procedure uses extremely low temperatures generated by liquid nitrogen (LN2) to freeze and destroy the target tissue, without the need for an additional gas. | Procedure or surgery | – |
| Breast Surgery (Lumpectomy or Mastectomy)Surgery can be performed as lumpectomy or mastectomy and axillary surgery, preferably sentinel lymph node biopsy. | Procedure or surgery | Breast Surgery (Lumpectomy or Mastectomy) |
Primary outcome
Locoregional recurrence (LRR)
Time frame: 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
Time frame: 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
6 secondary outcomes
Locoregional recurrence (LRR)
Time frame: 1 year
Disease-free survival (DFS)
Time frame: 5 years
Overall Survival (OS)
Time frame: 5 years
Circulating tumor cells (CTCs)
Time frame: 1 year
Patient satisfaction
Time frame: 1 month
EQ-5D questionnaire
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vanessa Monteiro Sanvido, PhD principal investigator
Research Institute - Hospital do Coracao
Afonso Celso Pinto Nazário, PhD principal investigator
Research Institute - Hospital do Coracao
Alexandre Biasi Cavalcante, PhD study director
Research Institute - Hospital do Coracao
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cryoablation and Breast Surgery (Lumpectomy or Mastectomy) in people with Breast Cancer and Breast Neoplasm, run by Hospital do Coracao at 2 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vanessa Monteiro Sanvido, PhD, Professor (+55 11 5576484, dravanessasanvido@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Locoregional recurrence (LRR) (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2025.