Early-Stage Breast CancerPhase 3CRYSTALNCT07483996
Cryoablation Versus Lumpectomy in Early-Stage Breast Cancer
A Phase 3 study testing Percutaneous cryoablation and Breast-conserving surgery in people with Early-Stage Breast Cancer, run by Franciscus Gasthuis & Vlietland (Hospital).
Trial summary
The goal of this randomised controlled trial is to compare ipsilateral breast cancer recurrence rates in patients with early-stage breast cancer between patients treated with breast conserving surgery and patient treated with percutaneous cryo-ablation. Read more about this study
- Who is it for?
- Ages 60 years and older, women only
- Conditions the study is for
- Early-Stage Breast Cancer
- What is being tested?
- Percutaneous cryoablation and Breast-conserving surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 938 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2026to 31 Dec 2038
- 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 60 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women
- Age > 60 years
- Postmenopausal (no menstrual period for at least 12 months or in case of an intra-uterine device (IUD) hormone levels that indicate the menopause: follicle stimulating hormone (FSH) > 20 IE/l and estradiol < 100 pmol/l)
- Histopathological confirmed primary invasive ER+/HER2- type breast cancer
- Bloom Richardson grade 1 or 2 (low or intermediate malignancy grade)
- Unilateral and unifocal breast cancer
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- A clinical T1N0M0 tumor (≤ 2cm and N0 on US and/or MRI), without distant metastases. The largest diameter measured will be used to determine eligibility.
- Tumor should be visible and well delineated (all borders of the tumor should be visible) on ultrasound at diagnosis and during the procedure.
- Sufficient knowledge of the Dutch language to complete the questionnaires
- To be able to give written informed consent
Who cannot join
- History of invasive breast cancer
- Breast augmentation
- BRCA-1 or 2 gene mutation carrier
- Lobular carcinoma
- Triple negative breast cancer
- Multifocality
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- HER2-neu overexpressing tumors
- Lymph vascular invasion (LVI) on core needle biopsy or histopathological confirmed after lumpectomy
- Indication for neoadjuvant systemic therapy
- Intraductal component > 25% of the diameter of the invasive tumor on MRI, complete area of the primary tumor should not exceed 2cm.
- Allergic to local anesthetics
- Electrical devices and/or implants that are not compatible with MRI
- Current severe breast infection
- Uncorrectable coagulopathy
- Hemodynamic instability
- Respiratory instability
- Refraining from adjuvant radiotherapy
- Indication for oncoplastic surgery (surgical volume replacement techniques e.g. LICAP)
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Cryoablation as Alternative for Lumpectomy in Early-Stage Breast Cancer: The CRYSTAL Trial
The goal of this randomised controlled trial is to compare ipsilateral breast cancer recurrence rates in patients with early-stage breast cancer between patients treated with breast conserving surgery and patient treated with percutaneous cryo-ablation.
- Conditions
- Early-Stage Breast Cancer
- Being tested
- Percutaneous cryoablation, Breast-conserving surgery
- Keywords
- Breast Cancer, Early-Stage Breast Cancer, Borstkanker, Vroegstadium Borstkanker
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Percutaneous cryoablationProcedure or surgery
Also called Minimally invasive treatment, Thermal ablation, Thermoablation
In this trial, the IceCure Prosense Cryoablation System will be used to execute the percutaneous cryoablation procedure.
Breast-conserving surgeryProcedure or surgery
Also called Lumpectomy, Lumpectomie
Breast-conserving surgery
| Study group | Role | What they receive |
|---|---|---|
| Patients will be treated with ultrasound-guided percutaneous cryoablation | Active comparator | Ultrasound-guided percutaneous cryoablation Receives: Procedure: Percutaneous cryoablation |
| Breast-conserving surgery | Other | Patients will be treated with breast-conserving surgery. Receives: Procedure: Breast-conserving surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ipsilateral breast cancer recurrence
Proportion of ipsilateral breast cancer recurrences (IBTR) after 5 years in both study arms.
Measured: Until 5 years after the intervention
Secondary outcomes (14)
Complication Rate
The proportion of complications within 30 days (percentage Clavien-Dindo classification).
Measured: Within 30 days after the intervention
Regional breast cancer recurrences
Regional breast cancer recurrences, defined as clinically, radiologically, and/or histologically confirmed recurrence in regional lymph nodes.
Measured: Until 5 years after the intervention
Disease Free Survival
Disease free survival (DFS) is defined as the time from date of intervention to the first occurrence of recurrent disease of the same histological characteristics as the primary tumor and in the same quadrant as the primary tumor
Measured: until 15 years after the intervention
Overall Survival
Overall survival (OS) is defined as the time from breast cancer diagnosis to death from any cause.
Measured: through study completion, an average of 15 years
Cosmetic Outcomes
- assess cosmetic outcomes following treatment with cryoablation or lumpectomy using the BCTOS-13 and BREAST-Q questionnaires at specified follow-up visits, and objective assessment using BCCT.core software. Higher scores indicate better cosmetic outcomes.
Measured: at baseline, 6 months and 1 year after the intervention
Hospital-related costs
Hospital-related costs, including expenses made due to additional findings on inclusion MRI
Measured: Until 5 years after the intervention
Out-of-hospital (non)-medical costs
To assess out-of-hospital medical and non-medical costs and productivity losses using the iMTA Medical Consumption Questionnaire (iMCQ) and iMTA Productivity Cost Questionnaire (iPCQ) questionnaires.
Measured: Until 5 years after the intervention
Generic Health-related Quality of Life
To assess general health-related quality of life using the EQ-5D-5L questionnaire, with higher scores indicating better health status
Measured: At baseline, 6 months after the intervention, 1 and 5 years after the intervention
Disease-specific quality of life
To assess cancer-specific quality of life using the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires. Higher scores indicate better functioning or greater symptom burden depending on the subscale.
Measured: At baseline, 6 months after the intervention, 1 and 5 years after the intervention
Complete ablation rate
On magnetic resonance imaging
Measured: 2 weeks after the intervention (cryoablation)
Predictive value of MRI
The negative predictive-, and diagnostic value of MRI for incomplete ablation
Measured: until 5 years after the intervention
Proportion of reinterventions
For both study arms.
Measured: For the duration of the study, most likely within 2 weeks after the intervention
Radiation Toxicity
The proportion of acute and long-term breast irradiation toxicity (radiation dermatitis, superficial or deep connective tissue fibrosis, chest wall pain, localized edema) using common toxicity criteria (CTCAE v5.0) and cosmetic questionnaires
Measured: At baseline, prior to radiation, 1 year and 5 years after the intervention
Incremental cost-utility ratio (ICUR)
To estimate the incremental cost-utility ratio (ICUR). Higher ICUR values indicate higher costs per quality-adjusted life year (QALY) gained.
Measured: Until 5 years after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2026
- Study start1 Apr 2026 (estimated)
- Primary completion31 Dec 2035 (estimated)
- Study completion31 Dec 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early-Stage 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
- Crossover
- Model description
- This is a multicenter randomized phase III non-inferiority trial with two arms: percutaneous cryoablation and breastconserving surgery. The randomization ratio is 1:1, stratified by center, tumor size (\< / \> 1 cm) and Bloom Richardson grade. All eligible patients will consecutively be included and randomized. Crossover is only possible for patients allocated to the cryoablation arm.
- Masking
- None (open label)
- Enrolment
- 938 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Franciscus Gasthuis & Vlietland (Hospital)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Linda Riks, Franciscus Gasthuis & Vlietland (Hospital)
- Investigators
- T.M.A.L. GE Klem, MD, PhD, Principal investigator, Franciscus Gasthuis & Vlietland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07483996
- Sponsor's protocol ID
- NL-010714
- Acronym
- CRYSTAL
- Status last verified
- Mar 2026
- First submitted
- 11 Mar 2026
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cryoablation as Alternative for Lumpectomy in Early-Stage Breast Cancer: The CRYSTAL Trial
- ClinicalTrials.gov ID
- NCT07483996
- Acronym / sponsor ID
- CRYSTAL / NL-010714
- Conditions
- Early-Stage Breast Cancer
- Keywords
- Breast Cancer, Early-Stage Breast Cancer, Borstkanker, Vroegstadium Borstkanker
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 938 participants (estimated)
- Lead sponsor
- Franciscus Gasthuis & Vlietland (Hospital)University, hospital or other
- Study start
- 1 Apr 2026 (estimated)
- Primary completion
- 31 Dec 2035 (estimated)
- Study completion
- 31 Dec 2038 (estimated)
- First posted
- 19 Mar 2026 (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.
The goal of this randomised controlled trial is to compare ipsilateral breast cancer recurrence rates in patients with early-stage breast cancer between patients treated with breast conserving surgery and patient treated with percutaneous cryo-ablation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a multicenter randomized phase III non-inferiority trial with two arms: percutaneous cryoablation and breastconserving surgery. The randomization ratio is 1:1, stratified by center, tumor size (< / > 1 cm) and Bloom Richardson grade. All eligible patients will consecutively be included and randomized. Crossover is only possible for patients allocated to the cryoablation arm.
| Arm | Type | Receives |
|---|---|---|
| Patients will be treated with ultrasound-guided percutaneous cryoablation | Active comparator | Procedure: Percutaneous cryoablationUltrasound-guided percutaneous cryoablation |
| Breast-conserving surgery | Other | Procedure: Breast-conserving surgeryPatients will be treated with breast-conserving surgery. |
Who may qualify
- Ages
- 60 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Women
- Age > 60 years
- Postmenopausal (no menstrual period for at least 12 months or in case of an intra-uterine device (IUD) hormone levels that indicate the menopause: follicle stimulating hormone (FSH) > 20 IE/l and estradiol < 100 pmol/l)
- Histopathological confirmed primary invasive ER+/HER2- type breast cancer
- Bloom Richardson grade 1 or 2 (low or intermediate malignancy grade)
Key exclusion criteria (18 listed)
- History of invasive breast cancer
- Breast augmentation
- BRCA-1 or 2 gene mutation carrier
- Lobular carcinoma
- Triple negative breast cancer
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 |
|---|---|---|
| Percutaneous cryoablationAlso: Minimally invasive treatment, Thermal ablation, ThermoablationIn this trial, the IceCure Prosense Cryoablation System will be used to execute the percutaneous cryoablation procedure. | Procedure or surgery | Patients will be treated with ultrasound-guided percutaneous cryoablation |
| Breast-conserving surgeryAlso: Lumpectomy, LumpectomieBreast-conserving surgery | Procedure or surgery | Breast-conserving surgery |
Primary outcome
Ipsilateral breast cancer recurrence
Time frame: Until 5 years after the intervention
Proportion of ipsilateral breast cancer recurrences (IBTR) after 5 years in both study arms.
14 secondary outcomes
Complication Rate
Time frame: Within 30 days after the intervention
Regional breast cancer recurrences
Time frame: Until 5 years after the intervention
Disease Free Survival
Time frame: until 15 years after the intervention
Overall Survival
Time frame: through study completion, an average of 15 years
Cosmetic Outcomes
Time frame: at baseline, 6 months and 1 year after the intervention
Hospital-related costs
Time frame: Until 5 years after the intervention
Out-of-hospital (non)-medical costs
Time frame: Until 5 years after the intervention
Generic Health-related Quality of Life
Time frame: At baseline, 6 months after the intervention, 1 and 5 years after the intervention
Disease-specific quality of life
Time frame: At baseline, 6 months after the intervention, 1 and 5 years after the intervention
Complete ablation rate
Time frame: 2 weeks after the intervention (cryoablation)
Predictive value of MRI
Time frame: until 5 years after the intervention
Proportion of reinterventions
Time frame: For the duration of the study, most likely within 2 weeks after the intervention
Radiation Toxicity
Time frame: At baseline, prior to radiation, 1 year and 5 years after the intervention
Incremental cost-utility ratio (ICUR)
Time frame: Until 5 years after the intervention
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 19 Mar 2026.
- Individual participant dataSharing planned: Undecided
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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.
T.M.A.L. GE Klem, MD, PhD principal investigator
Franciscus Gasthuis & Vlietland
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Percutaneous cryoablation and Breast-conserving surgery in people with Early-Stage Breast Cancer, run by Franciscus Gasthuis & Vlietland (Hospital).
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 10 inclusion and 18 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: opening soon, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
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 Linda Riks, MD (010 - 893 6010, l.riks@franciscus.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ipsilateral breast cancer recurrence (time frame: Until 5 years after the intervention). 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 19 Mar 2026.