Higher Dose Preoperative taMOxifen in Premenopausal bREast Cancer Patients

Hormone Receptor-positive Breast Cancer Clinical Trial

— MORE-T  

Official title:

Higher Dose taMOxifen in Premenopausal bREast Cancer Patients: a preoperaTive Window Trial (MORE-T Trial)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04997941
• Other study ID #: MORE-T trial
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 21, 2021
• Est. completion date: December 31, 2028

Study information

• Verified date: April 2024
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 238
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 48 Years

Eligibility

Inclusion Criteria:

1. Histopathologically and immunohistochemically confirmed ER+ and HER2- Premenopausal BC patients

2. Tumor size >0.5cm on USG

3. Stage I-IIIA BC and planned curative surgery

4. ECOG 0-2

5. Patients with adequate bone marrow function

• Hemoglobin > 10 g/dL, Plt > 100,000/mm3

6. Patients with adequate kidney function

• serum Cr = 1.4 mg/dL

7. 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

8. Patients who decided to voluntarily participate in this trial with written informed consent

9. 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

Exclusion Criteria:

1. Previous history of ipsilateral invasive breast cancer, in situ lesion

2. Previous history of chemotherapy or endocrine therapy on contralateral BC for the past 2 years

3. Patients who has distant metastasis

4. Patients who is pregnant or breastfeeding

5. Hormon receptor negative BC

6. Her-2 positive BC

7. Diagnosed pituitary adenoma

8. Women who has endometriosis, unknown vaginal bleeding

9. Inability to understand and willingness to sign a written informed consent

10. Patients with endometriosis or unexplained vaginal bleeding

11. Patients with a history of bleeding constitution, coagulopathy, or thromboembolism

12. Patients who have administered a CYP3A inhibitor or inducer, CYP2D6 inhibitor, etc. within 4 weeks prior to randomization

Related Conditions & MeSH terms

• Breast Neoplasms
• Hormone Receptor-positive Breast Cancer
• Premenopausal Breast Cancer

Intervention

Drug:
• Tamoxifen Oral Product
Experimental arm will have tamoxifen 40mg and active comparator arm will have tamoxifen 20mg for 14 days.

Diagnostic Test:
• Assessment of Ki-67
Paired biopsies (before and after tamoxifen therapy) will be required for the assessment of Ki-67.

Procedure:
• 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.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	After 14-day of tamoxifen treatment
Secondary	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.	After 14-day of tamoxifen treatment
Secondary	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%.	After 14-day of tamoxifen treatment
Secondary	AE	Adverse events	After 14-day of tamoxifen treatment
Secondary	SAE	Serious adverse events	After 14-day of tamoxifen treatment
Secondary	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).	After 14-day of tamoxifen treatment
Secondary	RFS	Relapse-free survival rate	5 years
Secondary	OS	Overall survival rate	5 years