Premenopausal Breast CancerPhase 2MORE-TNCT04997941
Higher Dose Preoperative taMOxifen in Premenopausal bREast Cancer Patients
A Phase 2 study testing Tamoxifen Oral Product, Assessment of Ki-67 and Surgery in people with Premenopausal Breast Cancer and Hormone Receptor-positive Breast Cancer, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
MORE-T trial is designed to investigate the effect of Tamoxifen 40mg (vs. Tamoxifen 20mg) for 2wks in presurgical setting. The greater reduction in Ki-67 might be observed in Tamoxifen 40mg arm compared to the Tamoxifen 20mg arm. Open Label, Phase 2, Randomized with 1:1 allocation Read more about this study
- Who is it for?
- Ages 20 to 48 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Premenopausal Breast Cancer, Hormone Receptor-positive Breast Cancer
- What is being tested?
- Tamoxifen Oral Product, Assessment of Ki-67 and Surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 238 participants
- Where
- 1 siteSouth Korea
- Study dates
- 21 Oct 2021to 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 20 to 48 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Histopathologically and immunohistochemically confirmed ER+ and HER2- Premenopausal BC patients
- Tumor size >0.5cm on USG
- Stage I-IIIA BC and planned curative surgery
- ECOG 0-2
- Patients with adequate bone marrow function
- Hemoglobin > 10 g/dL, Plt > 100,000/mm3
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- Patients with adequate kidney function
- serum Cr ≤ 1.4 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: ≤ 1.8 times of upper normal limit
- Patients who decided to voluntarily participate in this trial with written informed consent
- Premenopausal women : women who has not removed both ovaries, women who had menses in recent 1 year and FSH level is less than 30mIU/ml
Who cannot join
- Previous history of ipsilateral invasive breast cancer, in situ lesion
- Previous history of chemotherapy or endocrine therapy on contralateral BC for the past 2 years
- Patients who has distant metastasis
- Patients who is pregnant or breastfeeding
- Hormon receptor negative BC
- Her-2 positive BC
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- Diagnosed pituitary adenoma
- Women who has endometriosis, unknown vaginal bleeding
- Inability to understand and willingness to sign a written informed consent
- Patients with endometriosis or unexplained vaginal bleeding
- Patients with a history of bleeding constitution, coagulopathy, or thromboembolism
- Patients who have administered a CYP3A inhibitor or inducer, CYP2D6 inhibitor, etc. within 4 weeks prior to randomization
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Higher Dose taMOxifen in Premenopausal bREast Cancer Patients: a preoperaTive Window Trial (MORE-T Trial)
MORE-T trial is designed to investigate the effect of Tamoxifen 40mg (vs. Tamoxifen 20mg) for 2wks in presurgical setting.
The greater reduction in Ki-67 might be observed in Tamoxifen 40mg arm compared to the Tamoxifen 20mg arm.
Open Label, Phase 2, Randomized with 1:1 allocation
Read the detailed description
Tamoxifen
- Selective estrogen receptor modulator
- It has been the main endocrine treatment for decades
- Tamoxifen is a major endocrine treatment option, particularly for women who still have a significant ovarian estrogenic activity that cannot be controlled by aromatase inhibitors.
- The prospective clinical trials have shown that tamoxifen 20mg has comparable efficacy against tamoxifen 40mg with fewer toxicities in breast cancer patients. However, most of the trials comparing tamoxifen 20mg and 40mg were done in postmenopausal women.
- Previous studies have suggested that the higher dose of tamoxifen can induce higher serum levels of the drugs, and increasing tamoxifen dose up to 40mg can induce clinical responses in tumors resistant to 20mg of tamoxifen. A recent prospective trial demonstrated that increasing the dose of tamoxifen from 20 mg to 40 mg can compensate for the reduced endoxifen level in intermediate or poor metabolizer tamoxifen metabolizers based on CYP2D6 genotyping.
Ki-67
- Ki-67 antigen, a nuclear antigen, and marker of cell proliferation, is expressed during all cell-cycle phases except for G0, with levels peaking during mitosis.
- Reduction in Ki67 expression is reported to correlate with treatment response to endocrine therapy in ER+ breast cancer, and Ki-67 in short-term neoadjuvant studies has been shown to predict outcome in long-term adjuvant trials.
As the investigators have a higher proportion of young aged, premenopausal breast cancer patients in Korea, the investigators had an opportunity to examine the prognostic impact of young age in breast cancer recurrences and survivals. The institutional database and the Korean nationwide breast cancer registry data have all shown that the poor prognostic effect of a young age was exclusively seen in women with hormone receptor-positive breast cancers, and the effect was potentially due to the resistance to the tamoxifen. As therapeutic options diversify, studies on factors predictive of sensitivity to various endocrine therapies are needed to help select the appropriate treatment for young premenopausal breast cancer patients.
- Being tested
- Tamoxifen Oral Product, Assessment of Ki-67, Surgery
- Keywords
- Premenopausal Breast Cancer, Ki-67, Hormone Receptor-positive Breast Cancer, Tamoxifen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tamoxifen Oral ProductDrug
Also called Tamoxifen 40mg vs. 20mg
Experimental arm will have tamoxifen 40mg and active comparator arm will have tamoxifen 20mg for 14 days.
Assessment of Ki-67Diagnostic test
Paired biopsies (before and after tamoxifen therapy) will be required for the assessment of Ki-67.
SurgeryProcedure or surgery
The surgery date should be fixed before randomization. The surgery is to be performed within 1 day after the last dose of study treatment.
| Study group | Role | What they receive |
|---|---|---|
| Tamoxifen 40mg | Experimental | Tamoxifen 20mg b.i.d - Participants will be treated for 14 days. Receives: Drug: Tamoxifen Oral Product; Diagnostic Test: Assessment of Ki-67; Procedure: Surgery |
| Tamoxifen 20mg | Active comparator | Tamoxifen 10mg b.i.d - Participants will be treated for 14 days. Receives: Drug: Tamoxifen Oral Product; Diagnostic Test: Assessment of Ki-67; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Ki-67 level
Change in Ki67 (percentage of positive tumor cells tested by immunohistochemistry [IHC] - digital Image Analysis ) after a 14-day treatment period compared to baseline.
Measured: After 14-day of tamoxifen treatment
Secondary outcomes (7)
Changes in Ki67 according to CYP2D6 genotyping
Change in Ki67 (percentage of positive tumor cells tested by immunohistochemistry [IHC]) after a 14-day treatment period compared to baseline according to CYP2D6 genotyping.
Measured: After 14-day of tamoxifen treatment
The proportion of participants with relative decrease from baseline of Ki-67 ≥50%
The proportion of participants with relative decrease from baseline of Ki-67 (% positive tumor cells) ≥50%.
Measured: After 14-day of tamoxifen treatment
AE
Adverse events
Measured: After 14-day of tamoxifen treatment
SAE
Serious adverse events
Measured: After 14-day of tamoxifen treatment
PEPI (Preoperative Endocrine Prognostic Index) score
The PEPI score (ranged 0 to 12, lower score mean a better outcome) is the sum of the risk points of the pathological tumor (pT) stage, the pathological node (pN) stage, Ki67 levels and ER status (Allred score).
Measured: After 14-day of tamoxifen treatment
RFS
Relapse-free survival rate
Measured: 5 years
OS
Overall survival rate
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2021
- Study start21 Oct 2021
- Primary completion31 Dec 2024 (estimated)
- 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 Premenopausal 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 238 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hyeong-Gon Moon, Seoul National University Hospital
- Investigators
- Hyeong-Gon Moon, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04997941
- Sponsor's protocol ID
- MORE-T trial
- Acronym
- MORE-T
- Status last verified
- Apr 2024
- First submitted
- 23 Jul 2021
- Last updated
- 23 Apr 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 23 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Higher Dose taMOxifen in Premenopausal bREast Cancer Patients: a preoperaTive Window Trial (MORE-T Trial)
- ClinicalTrials.gov ID
- NCT04997941
- Acronym / sponsor ID
- MORE-T / MORE-T trial
- Keywords
- Premenopausal Breast Cancer, Ki-67, Hormone Receptor-positive Breast Cancer, Tamoxifen
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 238 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- 21 Oct 2021 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 10 Aug 2021 (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.
MORE-T trial is designed to investigate the effect of Tamoxifen 40mg (vs. Tamoxifen 20mg) for 2wks in presurgical setting.
The greater reduction in Ki-67 might be observed in Tamoxifen 40mg arm compared to the Tamoxifen 20mg arm.
Open Label, Phase 2, Randomized with 1:1 allocation
Detailed description
Tamoxifen
- Selective estrogen receptor modulator
- It has been the main endocrine treatment for decades
- Tamoxifen is a major endocrine treatment option, particularly for women who still have a significant ovarian estrogenic activity that cannot be controlled by aromatase inhibitors.
- The prospective clinical trials have shown that tamoxifen 20mg has comparable efficacy against tamoxifen 40mg with fewer toxicities in breast cancer patients. However, most of the trials comparing tamoxifen 20mg and 40mg were done in postmenopausal women.
- Previous studies have suggested that the higher dose of tamoxifen can induce higher serum levels of the drugs, and increasing tamoxifen dose up to 40mg can induce clinical responses in tumors resistant to 20mg of tamoxifen. A recent prospective trial demonstrated that increasing the dose of tamoxifen from 20 mg to 40 mg can compensate for the reduced endoxifen level in intermediate or poor metabolizer tamoxifen metabolizers based on CYP2D6 genotyping.
Ki-67
- Ki-67 antigen, a nuclear antigen, and marker of cell proliferation, is expressed during all cell-cycle phases except for G0, with levels peaking during mitosis.
- Reduction in Ki67 expression is reported to correlate with treatment response to endocrine therapy in ER+ breast cancer, and Ki-67 in short-term neoadjuvant studies has been shown to predict outcome in long-term adjuvant trials.
As the investigators have a higher proportion of young aged, premenopausal breast cancer patients in Korea, the investigators had an opportunity to examine the prognostic impact of young age in breast cancer recurrences and survivals. The institutional database and the Korean nationwide breast cancer registry data have all shown that the poor prognostic effect of a young age was exclusively seen in women with hormone receptor-positive breast cancers, and the effect was potentially due to the resistance to the tamoxifen. As therapeutic options diversify, studies on factors predictive of sensitivity to various endocrine therapies are needed to help select the appropriate treatment for young premenopausal breast cancer patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tamoxifen 40mg | Experimental | Drug: Tamoxifen Oral Product, Diagnostic Test: Assessment of Ki-67, Procedure: SurgeryTamoxifen 20mg b.i.d - Participants will be treated for 14 days. |
| Tamoxifen 20mg | Active comparator | Drug: Tamoxifen Oral Product, Diagnostic Test: Assessment of Ki-67, Procedure: SurgeryTamoxifen 10mg b.i.d - Participants will be treated for 14 days. |
Who may qualify
- Ages
- 20 to 48 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Histopathologically and immunohistochemically confirmed ER+ and HER2- Premenopausal BC patients
- Tumor size >0.5cm on USG
- Stage I-IIIA BC and planned curative surgery
- ECOG 0-2
- Patients with adequate bone marrow function
Key exclusion criteria (12 listed)
- Previous history of ipsilateral invasive breast cancer, in situ lesion
- Previous history of chemotherapy or endocrine therapy on contralateral BC for the past 2 years
- Patients who has distant metastasis
- Patients who is pregnant or breastfeeding
- Hormon receptor negative BC
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 |
|---|---|---|
| Tamoxifen Oral ProductAlso: Tamoxifen 40mg vs. 20mgExperimental arm will have tamoxifen 40mg and active comparator arm will have tamoxifen 20mg for 14 days. | Drug | Tamoxifen 20mg, Tamoxifen 40mg |
| Assessment of Ki-67Paired biopsies (before and after tamoxifen therapy) will be required for the assessment of Ki-67. | Diagnostic test | Tamoxifen 20mg, Tamoxifen 40mg |
| SurgeryThe surgery date should be fixed before randomization. The surgery is to be performed within 1 day after the last dose of study treatment. | Procedure or surgery | Tamoxifen 20mg, Tamoxifen 40mg |
Primary outcome
Changes in Ki-67 level
Time frame: After 14-day of tamoxifen treatment
Change in Ki67 (percentage of positive tumor cells tested by immunohistochemistry [IHC] - digital Image Analysis ) after a 14-day treatment period compared to baseline.
7 secondary outcomes
Changes in Ki67 according to CYP2D6 genotyping
Time frame: After 14-day of tamoxifen treatment
The proportion of participants with relative decrease from baseline of Ki-67 ≥50%
Time frame: After 14-day of tamoxifen treatment
AE
Time frame: After 14-day of tamoxifen treatment
SAE
Time frame: After 14-day of tamoxifen treatment
PEPI (Preoperative Endocrine Prognostic Index) score
Time frame: After 14-day of tamoxifen treatment
RFS
Time frame: 5 years
OS
Time frame: 5 years
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 23 Apr 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.
Hyeong-Gon Moon 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 Tamoxifen Oral Product, Assessment of Ki-67 and Surgery in people with Premenopausal Breast Cancer and Hormone Receptor-positive 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 14 inclusion and 12 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 23 Apr 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?
Changes in Ki-67 level (time frame: After 14-day of tamoxifen treatment). 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 23 Apr 2024.