Breast CancerPhase 2NCT03900637
PersonaLized neoAdjuvant Strategy ER Positive and HER2 Negative Breast Cancer TO Increase BCS Rate
A Phase 2 study testing Leuprorelin acetate, Letrozole and MammaPrint in people with Breast Cancer, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
In ER+ and HER2- breast cancer(BC) patients for whom BCS is not feasible, we investigate the rate of BCS can be increased while decreasing unnecessary chemotherapy thru selective neoadjuvant chemotherapy or neoadjuvant endocrine therapy using tools of nodal status, Ki-67, and multigene assay(Mammaprint) Read more about this study
- Who is it for?
- Ages 19 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Leuprorelin acetate, Letrozole and MammaPrint
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 1 siteSouth Korea
- Study dates
- 8 Nov 2019to 31 Dec 2028
- Phase
- Phase 2
- 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 19 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histopathologically and immunohistochemically confirmed ER+ and HER2- BC patients
- Stage I-IIIA BC patients with detectable tumor sizes
- BC patients for whom BCS is not feasible due to tumor sizes or locations (two surgeons at each institution evaluate the infeasibility of BCS)
- Patients without distant metastasis which were identified pathologically or radiologically
- Female patients ≥ 19 years
- Diagnosis of menopause is defined as no menstruation for 1-year or both ovaries removed surgically
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- ECOG 0-2
- Patients with adequate bone marrow function
- Hemoglobin 10 g/dL, ANC 1,500/mm3, Plt 100,000/mm3
- Patients with adequate kidney function
- serum Cr ≤ 1.5 mg/dL
- Patients with adequate liver function
- Bilirubin: ≤ 1.5 times of upper normal limit
- AST/ALT: ≤ 1.5 times of upper normal limit
- Alkaline phosphatase: ≤ 1.5 times of upper normal limit
- Patients who decided to voluntarily participate in this trial with written informed consent
Who cannot join
- History of treatment for ipsilateral BC or breast carcinoma in situ
- Confirmed distant metastasis of BC
- History of cancer other than BC
- Pregnant (positive pregnancy test within a week of enrollment) or breast-feeding patients
- Uncontrolled severe infection
- Psychiatric illness or epilepsy
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- Male BC patients
- Inability to understand and willingness to sign a written informed consent
- Mammographic extensive microcalcification
- Multicentral, Bilateral BC
- History of chemotherapy or endocrine therapy on contralateral BC for the past 2 years
- ER-
- HER2+
- Undetectable and unmeasurable primary tumor size
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multi-institutional Study to Increase Breast Conserving Surgery (BCS) Rate With Personalized Neoadjuvant Strategy in ER Positive and HER2 Negative Breast Cancer Patients for Whom BCS is Not Feasible
In ER+ and HER2- breast cancer(BC) patients for whom BCS is not feasible, we investigate the rate of BCS can be increased while decreasing unnecessary chemotherapy thru selective neoadjuvant chemotherapy or neoadjuvant endocrine therapy using tools of nodal status, Ki-67, and multigene assay(Mammaprint)
Read the detailed description
In patients with resectable BC, the neoadjuvant chemotherapy is recognized as one of the standard therapy in order to control and prevent the micrometastasis.
Conducting neoadjuvant chemotherapy can lead to increased numbers of BCS compared with adjuvant chemotherapy and the prognosis of BC patients is known to be improved when there is pathological complete response (pCR) after neoadjuvant chemotherapy compared with no pCR.
The effect of neoadjuvant chemotherapy is different in breast cancer subtypes. The quasi-pCR in HR- HER2+ BC is reported as 67% while 37% and 13% in triple negative and HR+ HER2- BC, respectively and it indicates that neoadjuvant chemotherapy has only limited effect in HR+ BC and the declined quality of life and the fecundity loss due to chemotherapy is a serious socioeconomic loss, especially in young patients.
According to the SOFT trial, for high risk, pre-menopausal women, use of exmestane (AI, Aromatase Inhibitors) and ovarian suppression as adjuvant systemic therapy did improve the PFD compared with the use of tamoxifen and ovarian suppression.
Neoadjuvant hormonal therapy as well as neoadjuvant chemotherapy has benefits in making inoperable BC to operable BC and improving the possibility of BCS by reducing the tumor size with complete response or partial response. Although these neoadjuvant systemic therapies have an ultimate objective to reduce the recurrence rate and improve the survival rate, the overall survival and disease-free survival has been reported similar to adjuvant systemic therapies. The clinical response rate of neoadjuvant hormonal therapy ranged from 13.5% to 100%, the radiologic response rate by ultrasound ranged from 20% to 91.7%, and these are statistically similar to the response rate of the neoadjuvant chemotherapy in ER+ patients. Most studies where letrozole was tested among AIs showed that letrozole has a similar or a little better effect on clinical or radiological response rate over tamoxifen and there were statistically more patients who became operable or eligible for BCS after neoadjuvant chemotherapy. Comparison studies among AIs showed that the response rates have been best achieved in letrozole over anastrozole and exemestane and the BCS rate was lowest in letrozole without statistical significance. According to the standard treatment guideline suggesting the selective use of ovarian suppression along with tamoxifen in HR+, premenopausal patients, a study investigated the combined treatment of letrozole with reversible ovarian ablation using goserelin (luteinizing hormone-releasing hormone: LHRH). The results showed that the response rate of the combination treatment of goserelin and anastrozole for 24 weeks as neoadjuvant hormonal therapy was statistically superior to goserelin and tamoxifen in premenopausal BC patients and this was not observed in the adjuvant setting. The most commonly used agents in BC are goserelin and leuprorelin(Leuplin) and their mechanism of action is to desensitize the hypothalamus and suppress the ovarian function by reducing the secretion of LH and FSH.
MammaPrint, which analyses 70-gene expressed in breast cancer, can identify low risk patients who may safely forgo chemotherapy and high risk patients who can benefit from chemotherapy. Recent results from MINDACT trial have proved that 46.2% of HR+ and clinical high risk patients were classified into MammaPrint low risk and they could avoid unnecessary chemotherapy. In 2017 San Antonio breast cancer symposium, Dubsky et al. reported the analysis of correlation between neoadjuvant chemotherapy and score of Endopredict(EP) multigene assay in ER+ and HER2- patients treated on ABCSG 34. In neoadjuvant chemotherapy group, reduction of tumor size in patients with low EP score(Endopredict low risk group) was significantly low(NPV 100%). Meanwhile, in neoadjuvant hormonal therapy group, reduction of tumor size in patients with high EP score(Endopredict high risk group) was significantly low(NPV 92%). These results support the evidence that response of neoadjuvant chemotherapy or hormonal therapy can be predicted by the molecular score of tumor and selective treatment can maximize the effect.
Accordingly, in this study, patients with MammaPrint test is performed, neoadjuvant chemotherapy is conducted to genomic High Risk patients, and neoadjuvant endocrine therapy is conducted to Low Risk patients. Although adjuvant therapy is conducted after the completion of this study, in case there is progressive disease (PD) after neoadjuvant endocrine therapy, adjuvant chemotherapy is conducted.
- Conditions
- Breast Cancer
- Being tested
- Leuprorelin acetate, Letrozole, MammaPrint
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Leuprorelin acetateDrug
Also called Leuplin
In premenopausal women, 3.75mg of leuprorelin acetate is subcutaneously administered once every 4 weeks for 16 weeks. (if needed, maximum for 24 weeks)
LetrozoleDrug
Also called Lenara, Bretra
2.5 mg tablet is orally administered once a day, without regard to meals, for 16 weeks (if needed, maximum for 24 weeks)
MammaPrintGenetic
In this study, patients with MammaPrint test is performed, neoadjuvant chemotherapy is conducted to genomic High Risk patients, and neoadjuvant endocrine therapy is conducted to Low Risk patients.
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 1. MammaPrint high risk :
* Neoadjuvant chemotherapy : Adriamycin/Cyclophosphamide #4 followed by Docetaxel #4
2. MammaPrint low risk :
* Premenopausal women : Letrozole 2.5mg PO QD + leuprorelin acetate 3.6mg SQ every 4weeks during 16 weeks (if needed, maximum for 24 weeks)
* Postmenopausal women : Letrozole 2.5mg PO QD during 16 weeks (if needed, maximum for 24 weeks) Receives: Drug: Leuprorelin acetate; Drug: Letrozole; Genetic: MammaPrint |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conversion Rate
Evaluate the conversion rate from BCS-ineligible to BCS-eligible patients
Measured: 4 months(maximum 6 months)
Secondary outcomes (4)
Actual Conversion Rate
Evaluate the actual performance rate of BCS
Measured: 4 months(maximum 6 months)
pCR
Evaluate pathological complete response
Measured: 4 months(maximum 6 months)
cCR
Evaluate clinical response rate
Measured: 4 months(maximum 6 months)
Tumor Size Reduction Rate
Evaluate the accomplished rate of targeted tumor size reduction which enable to make BCS possible at presentation
Measured: 4 months(maximum 6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2019
- Study start8 Nov 2019
- Primary completion31 Oct 2023
- Study completion31 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.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 122 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wonshik Han, Seoul National University Hospital
- Investigators
- Wonshik Han, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03900637
- Sponsor's protocol ID
- PLATO study
- Status last verified
- Jul 2024
- First submitted
- 2 Apr 2019
- Last updated
- 31 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-institutional Study to Increase Breast Conserving Surgery (BCS) Rate With Personalized Neoadjuvant Strategy in ER Positive and HER2 Negative Breast Cancer Patients for Whom BCS is Not Feasible
- ClinicalTrials.gov ID
- NCT03900637
- Acronym / sponsor ID
- PLATO study
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 122 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- 8 Nov 2019 (actual)
- Primary completion
- 31 Oct 2023 (actual)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 3 Apr 2019 (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.
In ER+ and HER2- breast cancer(BC) patients for whom BCS is not feasible, we investigate the rate of BCS can be increased while decreasing unnecessary chemotherapy thru selective neoadjuvant chemotherapy or neoadjuvant endocrine therapy using tools of nodal status, Ki-67, and multigene assay(Mammaprint)
Detailed description
In patients with resectable BC, the neoadjuvant chemotherapy is recognized as one of the standard therapy in order to control and prevent the micrometastasis.
Conducting neoadjuvant chemotherapy can lead to increased numbers of BCS compared with adjuvant chemotherapy and the prognosis of BC patients is known to be improved when there is pathological complete response (pCR) after neoadjuvant chemotherapy compared with no pCR.
The effect of neoadjuvant chemotherapy is different in breast cancer subtypes. The quasi-pCR in HR- HER2+ BC is reported as 67% while 37% and 13% in triple negative and HR+ HER2- BC, respectively and it indicates that neoadjuvant chemotherapy has only limited effect in HR+ BC and the declined quality of life and the fecundity loss due to chemotherapy is a serious socioeconomic loss, especially in young patients.
According to the SOFT trial, for high risk, pre-menopausal women, use of exmestane (AI, Aromatase Inhibitors) and ovarian suppression as adjuvant systemic therapy did improve the PFD compared with the use of tamoxifen and ovarian suppression.
Neoadjuvant hormonal therapy as well as neoadjuvant chemotherapy has benefits in making inoperable BC to operable BC and improving the possibility of BCS by reducing the tumor size with complete response or partial response. Although these neoadjuvant systemic therapies have an ultimate objective to reduce the recurrence rate and improve the survival rate, the overall survival and disease-free survival has been reported similar to adjuvant systemic therapies. The clinical response rate of neoadjuvant hormonal therapy ranged from 13.5% to 100%, the radiologic response rate by ultrasound ranged from 20% to 91.7%, and these are statistically similar to the response rate of the neoadjuvant chemotherapy in ER+ patients. Most studies where letrozole was tested among AIs showed that letrozole has a similar or a little better effect on clinical or radiological response rate over tamoxifen and there were statistically more patients who became operable or eligible for BCS after neoadjuvant chemotherapy. Comparison studies among AIs showed that the response rates have been best achieved in letrozole over anastrozole and exemestane and the BCS rate was lowest in letrozole without statistical significance. According to the standard treatment guideline suggesting the selective use of ovarian suppression along with tamoxifen in HR+, premenopausal patients, a study investigated the combined treatment of letrozole with reversible ovarian ablation using goserelin (luteinizing hormone-releasing hormone: LHRH). The results showed that the response rate of the combination treatment of goserelin and anastrozole for 24 weeks as neoadjuvant hormonal therapy was statistically superior to goserelin and tamoxifen in premenopausal BC patients and this was not observed in the adjuvant setting. The most commonly used agents in BC are goserelin and leuprorelin(Leuplin) and their mechanism of action is to desensitize the hypothalamus and suppress the ovarian function by reducing the secretion of LH and FSH.
MammaPrint, which analyses 70-gene expressed in breast cancer, can identify low risk patients who may safely forgo chemotherapy and high risk patients who can benefit from chemotherapy. Recent results from MINDACT trial have proved that 46.2% of HR+ and clinical high risk patients were classified into MammaPrint low risk and they could avoid unnecessary chemotherapy. In 2017 San Antonio breast cancer symposium, Dubsky et al. reported the analysis of correlation between neoadjuvant chemotherapy and score of Endopredict(EP) multigene assay in ER+ and HER2- patients treated on ABCSG 34. In neoadjuvant chemotherapy group, reduction of tumor size in patients with low EP score(Endopredict low risk group) was significantly low(NPV 100%). Meanwhile, in neoadjuvant hormonal therapy group, reduction of tumor size in patients with high EP score(Endopredict high risk group) was significantly low(NPV 92%). These results support the evidence that response of neoadjuvant chemotherapy or hormonal therapy can be predicted by the molecular score of tumor and selective treatment can maximize the effect.
Accordingly, in this study, patients with MammaPrint test is performed, neoadjuvant chemotherapy is conducted to genomic High Risk patients, and neoadjuvant endocrine therapy is conducted to Low Risk patients. Although adjuvant therapy is conducted after the completion of this study, in case there is progressive disease (PD) after neoadjuvant endocrine therapy, adjuvant chemotherapy is conducted.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: Leuprorelin acetate, Drug: Letrozole, Genetic: MammaPrint1. MammaPrint high risk : * Neoadjuvant chemotherapy : Adriamycin/Cyclophosphamide #4 followed by Docetaxel #4 2. MammaPrint low risk : * Premenopausal women : Letrozole 2.5mg PO QD + leuprorelin acetate 3.6mg SQ every 4weeks during 16 weeks (if needed, maximum for 24 weeks) * Postmenopausal women : Letrozole 2.5mg PO QD during 16 weeks (if needed, maximum for 24 weeks) |
Who may qualify
- Ages
- 19 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histopathologically and immunohistochemically confirmed ER+ and HER2- BC patients
- Stage I-IIIA BC patients with detectable tumor sizes
- BC patients for whom BCS is not feasible due to tumor sizes or locations (two surgeons at each institution evaluate the infeasibility of BCS)
- Patients without distant metastasis which were identified pathologically or radiologically
- Female patients ≥ 19 years
Key exclusion criteria (14 listed)
- History of treatment for ipsilateral BC or breast carcinoma in situ
- Confirmed distant metastasis of BC
- History of cancer other than BC
- Pregnant (positive pregnancy test within a week of enrollment) or breast-feeding patients
- Uncontrolled severe infection
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 |
|---|---|---|
| Leuprorelin acetateAlso: LeuplinIn premenopausal women, 3.75mg of leuprorelin acetate is subcutaneously administered once every 4 weeks for 16 weeks. (if needed, maximum for 24 weeks) | Drug | Arm I |
| LetrozoleAlso: Lenara, Bretra2.5 mg tablet is orally administered once a day, without regard to meals, for 16 weeks (if needed, maximum for 24 weeks) | Drug | Arm I |
| MammaPrintIn this study, patients with MammaPrint test is performed, neoadjuvant chemotherapy is conducted to genomic High Risk patients, and neoadjuvant endocrine therapy is conducted to Low Risk patients. | Genetic | Arm I |
Primary outcome
Conversion Rate
Time frame: 4 months(maximum 6 months)
Evaluate the conversion rate from BCS-ineligible to BCS-eligible patients
4 secondary outcomes
Actual Conversion Rate
Time frame: 4 months(maximum 6 months)
pCR
Time frame: 4 months(maximum 6 months)
cCR
Time frame: 4 months(maximum 6 months)
Tumor Size Reduction Rate
Time frame: 4 months(maximum 6 months)
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 31 Jul 2024.
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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. This study is not recruiting at the moment.
Wonshik Han principal investigator
Seoul National University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Leuprorelin acetate, Letrozole and MammaPrint in people with Breast Cancer, run by Seoul National University Hospital at 1 site in South Korea.
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 16 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2024. 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 South Korea. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conversion Rate (time frame: 4 months(maximum 6 months)). 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 31 Jul 2024.