NCT04997941

Higher Dose Preoperative taMOxifen in Premenopausal bREast Cancer Patients

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 238 (estimated)
• Sponsor: Seoul National University Hospital · Academic / Other
• Sex: Female
• Age: 20 Years – 48 Years
• Healthy volunteers: Accepted

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

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.

Conditions

• Premenopausal Breast Cancer
• Hormone Receptor-positive Breast Cancer

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2021-10-21
• Primary completion: 2024-12-31
• Completion: 2028-12-31
• First posted: 2021-08-10
• Last updated: 2024-04-23

Locations

1 site across 1 country: South Korea