Breast CancerCRANBERRYNCT06813456
Implementation of Solid Digital PCR to Support Gold-standard Methods for Evaluation of HER2 Amplification Status: Focus on HER2-low Subtype
An observational study of Breast Cancer, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
Trial summary
The goal of the retrospective phase of this study is to validate the specificity and the sensitivity of two Real-Time quantitative PCR based techniques in order to support the gold-standard approaches used to evaluate the HER2 gene status in breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- How many people
- 234 participants
- Where
- 1 siteItaly
- Study dates
- 8 Nov 2024to 1 Dec 2028
- How long will I take part?
- 5 Years
- Phase
- Observational
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: The population considered for the retrospective phase of the study will consist of women with stage I-III breast cancer, aged 18 years and older, who have accessed the SSD of Breast Surgery and Oncology of IRCCS - Azienda Ospedaliero-Universitaria di Bologna Policlinico di S.Orsola, in the context of the normal care path provided for patients with this pathology (first histopathological diagnosis from 1/1/2022). The population considered for the prospective phase of the study will consist of women with early-stage HER2-0 and HER2-low breast cancer (population 1) or metastatic HER2-low breast cancer (population 2), 18 years of age and older, who will be referred to the SSD of Breast Surgery and Oncology of IRCCS - Azienda Ospedaliero-Universitaria di Bologna Policlinico di S.Orsola.
Who may be able to join
- Age ≥18 years
- Histologic confirmation of breast cancer from 1/1/2022
- Patient treated with systemic and surgical therapy (retrospective phase)
- Signed informed consent
- HER2-0 and/or HER2-low patient, according to IHC and D-DISH/FISH, treatable with systemic and surgical therapy (prospective phase)
Who cannot join
- Lack of molecular classification on the basis of prognostic-predictive markers ER, PR, Ki67 and HER2 (Luminal A, Luminal B HER2-positive, Luminal B HER2- negative, HER2-positive, Triple negative)
- Prior neoplasms, other than the neoplasm under investigation, arised within the past 5 years
- Missing histological diagnosis of HER2-0 and/or HER2-low breast cancer (prospective phase)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Bologna, Bologna, 40138
Sara Coluccelli, PhD, +393290928473, sara.coluccelli@aosp.bo.it
About this study
The goal of the retrospective phase of this study is to validate the specificity and the sensitivity of two Real-Time quantitative PCR based techniques in order to support the gold-standard approaches used to evaluate the HER2 gene status in breast cancer.
Furthemore, HER2-low patients are enrolled in a prospective phase, both in early stage and in case of recurrence, in order to monitorate HER2 expression levels changes under treatments by using liquid biopsy. The first aim is to be able to distinguish responders vs non-responders earlier than the standard monitoring through tumoral markers and medical examination.
Read the detailed description
The hypothesis underlying this study is that the use of solid digital PCR technology and the MammaTyper® diagnostic test allows the molecular classification of breast carcinomas to be refined and strengthened from early diagnosis, limiting the bias related to interpretation problems and thus improving the prognostic power of traditional clinical pathological parameters. In fact, the quantitative data of each individual marker, associated with the molecular subtype, provides the oncologist with indispensable prognostic information to define the most appropriate therapeutic approach.
Specifically, it is believed that the use of more accurate methods to define HER2 amplification status may help improve diagnostic accuracy, as well as support the choice of optimal therapy, especially for the new HER2-low tumour subtype.
It is believed that HER2 levels defined in this way, once correlated with clinical data on survival and response to the therapeutic regimen undertaken by each patient, will allow the detection of significant differences between the HER2-positive, -negative and -equivocal groups, the latter needing to be reclassified as separate entities.
A further hypothesis concerns the possible impact that dPCR technology may have in predicting and monitoring response to therapies in a robust, rapid and cost-effective manner. The first endpoint of this study is the identification, by quantitative analysis with dPCR and Mammatyper® performed on paraffin-embedded archival tissue, of HER2-amplified and -unamplified breast carcinomas, the expression levels of which will be compared with those detected by gold-standard methods in order to resolve cases that are difficult to interpret. With the molecular test Mammatyper® it will also be possible to objectively and reproducibly determine the expression of the prognostic-predictive markers ER, PR and Ki67. It is expected that the clinical outcomes of patients will correlate significantly with the expression levels of ER, PR, Ki67 and HER2 estimated in the study.
The second endpoint of the study is the identification, by quantitative dPCR analysis performed on paraffin-embedded tissue and liquid biopsy, of HER2-0 and HER2-low enrolled early-stage breast carcinomas undergoing surgical and systemic therapy.It is expected to detect any fluctuations in HER2 expression/amplification due to sensitivity/resistance to systemic therapy or, at follow-up, recurrence.
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, HER2, HER2-low, Prognostic-predictive markers, IHC, D-DISH, FISH, solid digital PCR, liquid biopsy
- Medical subject headings
- Breast Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Breast cancer patients undergone surgical and systemic therapy
Estimation of sensitivity and specificity confidence intervals of MammaTyper and dPCR threshold values in discriminating HER2 positivity on FFPE tissues and comparison with gold-standard approaches.
Measured: At baseline
Early-stage HER2-low breast cancer patients undergoing surgical and systemic therapy
Sensitivity and specificity of HER2 expression values according to dPCR performed on FFPE tissue and according to dPCR performed on liquid biopsy, compared with the gold-standard approaches
Measured: At baseline
Metastatic HER2-low patients in treatment with Trastuzumab-Deruxtecan
Response to Trastuzumab-Deruxtecan therapy to be assessed by tumor markers, radiological investigations and clinical evaluation.
Measured: Every 4 months from the start of therapy,assessed up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2025
- Study start8 Nov 2024
- Primary completion1 Nov 2025 (estimated)
- Study completion1 Dec 2028 (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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 234 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sara Coluccelli, PhD, Principal investigator, IRCCS Azienda Ospedaliero-Universitaria di Bologna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06813456
- Sponsor's protocol ID
- CRANBERRY
- Other IDs
- RC-2024-2790620
- Acronym
- CRANBERRY
- Status last verified
- Dec 2024
- First submitted
- 9 Dec 2024
- Last updated
- 7 Feb 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 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implementation of Solid Digital PCR to Support Gold-standard Methods for Evaluation of HER2 Amplification Status: Focus on HER2-low Subtype
- ClinicalTrials.gov ID
- NCT06813456
- Acronym / sponsor ID
- CRANBERRY / CRANBERRY
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, HER2, HER2-low, Prognostic-predictive markers, IHC, D-DISH, FISH, solid digital PCR
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 234 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- 8 Nov 2024 (actual)
- Primary completion
- 1 Nov 2025 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 7 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.
The goal of the retrospective phase of this study is to validate the specificity and the sensitivity of two Real-Time quantitative PCR based techniques in order to support the gold-standard approaches used to evaluate the HER2 gene status in breast cancer.
Furthemore, HER2-low patients are enrolled in a prospective phase, both in early stage and in case of recurrence, in order to monitorate HER2 expression levels changes under treatments by using liquid biopsy. The first aim is to be able to distinguish responders vs non-responders earlier than the standard monitoring through tumoral markers and medical examination.
Detailed description
The hypothesis underlying this study is that the use of solid digital PCR technology and the MammaTyper® diagnostic test allows the molecular classification of breast carcinomas to be refined and strengthened from early diagnosis, limiting the bias related to interpretation problems and thus improving the prognostic power of traditional clinical pathological parameters. In fact, the quantitative data of each individual marker, associated with the molecular subtype, provides the oncologist with indispensable prognostic information to define the most appropriate therapeutic approach.
Specifically, it is believed that the use of more accurate methods to define HER2 amplification status may help improve diagnostic accuracy, as well as support the choice of optimal therapy, especially for the new HER2-low tumour subtype.
It is believed that HER2 levels defined in this way, once correlated with clinical data on survival and response to the therapeutic regimen undertaken by each patient, will allow the detection of significant differences between the HER2-positive, -negative and -equivocal groups, the latter needing to be reclassified as separate entities.
A further hypothesis concerns the possible impact that dPCR technology may have in predicting and monitoring response to therapies in a robust, rapid and cost-effective manner. The first endpoint of this study is the identification, by quantitative analysis with dPCR and Mammatyper® performed on paraffin-embedded archival tissue, of HER2-amplified and -unamplified breast carcinomas, the expression levels of which will be compared with those detected by gold-standard methods in order to resolve cases that are difficult to interpret. With the molecular test Mammatyper® it will also be possible to objectively and reproducibly determine the expression of the prognostic-predictive markers ER, PR and Ki67. It is expected that the clinical outcomes of patients will correlate significantly with the expression levels of ER, PR, Ki67 and HER2 estimated in the study.
The second endpoint of the study is the identification, by quantitative dPCR analysis performed on paraffin-embedded tissue and liquid biopsy, of HER2-0 and HER2-low enrolled early-stage breast carcinomas undergoing surgical and systemic therapy.It is expected to detect any fluctuations in HER2 expression/amplification due to sensitivity/resistance to systemic therapy or, at follow-up, recurrence.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The population considered for the retrospective phase of the study will consist of women with stage I-III breast cancer, aged 18 years and older, who have accessed the SSD of Breast Surgery and Oncology of IRCCS - Azienda Ospedaliero-Universitaria di Bologna Policlinico di S.Orsola, in the context of the normal care path provided for patients with this pathology (first histopathological diagnosis from 1/1/2022). The population considered for the prospective phase of the study will consist of women with early-stage HER2-0 and HER2-low breast cancer (population 1) or metastatic HER2-low breast cancer (population 2), 18 years of age and older, who will be referred to the SSD of Breast Surgery and Oncology of IRCCS - Azienda Ospedaliero-Universitaria di Bologna Policlinico di S.Orsola.
Key inclusion criteria (5 listed)
- Age ≥18 years
- Histologic confirmation of breast cancer from 1/1/2022
- Patient treated with systemic and surgical therapy (retrospective phase)
- Signed informed consent
- HER2-0 and/or HER2-low patient, according to IHC and D-DISH/FISH, treatable with systemic and surgical therapy (prospective phase)
Key exclusion criteria (3 listed)
- Lack of molecular classification on the basis of prognostic-predictive markers ER, PR, Ki67 and HER2 (Luminal A, Luminal B HER2-positive, Luminal B HER2- negative, HER2-positive, Triple negative)
- Prior neoplasms, other than the neoplasm under investigation, arised within the past 5 years
- Missing histological diagnosis of HER2-0 and/or HER2-low breast cancer (prospective phase)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Breast cancer patients undergone surgical and systemic therapy
Time frame: At baseline
Estimation of sensitivity and specificity confidence intervals of MammaTyper and dPCR threshold values in discriminating HER2 positivity on FFPE tissues and comparison with gold-standard approaches.
Early-stage HER2-low breast cancer patients undergoing surgical and systemic therapy
Time frame: At baseline
Sensitivity and specificity of HER2 expression values according to dPCR performed on FFPE tissue and according to dPCR performed on liquid biopsy, compared with the gold-standard approaches
Metastatic HER2-low patients in treatment with Trastuzumab-Deruxtecan
Time frame: Every 4 months from the start of therapy,assessed up to 60 months
Response to Trastuzumab-Deruxtecan therapy to be assessed by tumor markers, radiological investigations and clinical evaluation.
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 7 Feb 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.
Sara Coluccelli, PhD principal investigator
IRCCS Azienda Ospedaliero-Universitaria di Bologna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
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 3 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 7 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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.
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 Sara Coluccelli, PhD (+393290928473, sara.coluccelli@aosp.bo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Breast cancer patients undergone surgical and systemic therapy (time frame: At baseline). The study lists 3 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 7 Feb 2025.