Efficacy of Tamoxifen Versus Toremifene in CYP2D6 IM/PM of Premenopausal Patients With ER-positive Early Breast Cancer

• Status: Recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

This clinical trial is designed to be a multi-center prospective, parallel-controlled Phase III clinical study. In this study, the efficacy of tamoxifen versus toremifene shall be compared in CYP2D6 intermediate/poor metabolizers of premenopausal patients with estrogen receptor-positive early breast cancer.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chinese Anti-Cancer Association
• Collaborators: Affiliated Hospital of Qinghai University; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; First Affiliated Hospital of Chongqing Medical University; First Hospital of China Medical University; First Hospital of Jilin University; Fudan University; Guangdong Provincial People's Hospital; Hainan People's Hospital; Harbin Medical University; Hebei Tumor Hospital; Henan Cancer Hospital; Hunan Cancer Hospital; Jiangsu Provincial People's Hospital; Southwest Hospital, China; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; The First Hospital of Jilin University; The Third Affiliated Hospital of Kunming Medical College.; The Third Affiliated Hospital of Nanchang University; Tianjin Medical University Cancer Institute and Hospital; Union hospital of Fujian Medical University; Wuhan TongJi Hospital; Zhejiang Cancer Hospital
• Treatments: Tamoxifen; Toremifene

Criteria

Inclusion Criteria:

1. Premenopausal women aged 18-50 years;

2. ECOG PS: 0-2 points;

3. Invasive breast cancer confirmed by histology with ER ≥ 10% (all test results should be reviewed and confirmed by Department of Pathology of the participant institution);

4. Participants have completed the standard local radical treatment (modified or conservative radical mastectomy) with or without neo-adjuvant/adjuvant chemotherapy or radiotherapy;

5. Participants must be able to understand this study and are willing to participate, agree to genotype screening and sign informed consent form with good compliance and cooperation in follow-ups;

6. Polymorphism analysis showed that patients are CYP2D6 * 4, * 5, * 10, * 14, * 17, * 41 allele carriers;

7. Hemoglobin ≥ 90g/L, neutrophils ≥ 1.5 × 109/L, platelets ≥ 75 × 109/L, AST and ALT ≤ 2.5 times the upper limit of normal (ULN), serum creatinine and urea nitrogen ≤ ULN.

Exclusion Criteria:

1. Patients have previously received neoadjuvant endocrine therapy or have started adjuvant endocrine therapy;

2. There are any comorbidities that may increase the level of sex hormones: such as pituitary adenomas, ovarian tumors, thymic carcinomas, etc.;

3. There are any comorbidities that may reduce the level of sex hormones such as hyperthyroidism, hypothyroidism, cirrhosis, severe malnutrition, Turner syndrome, lack of sex hormone synthetase, intracranial tumors, pituitary atrophy etc.;

4. Patients have undergone or planned to conduct ovariectomy or ovarian function inhibition;

5. Patients needs to take other medicines which can influence the activity of CYP2D6 (such as fluoxetine, paroxetine, quinidine, bupropion), CYP3A4 (such as erythromycin, acetylspiramycin, ritonavir, ketoconazole, nicardipine);

6. Patients have been treated with other trial medications in the past 2 weeks;

7. Pregnant or lactating women (women of childbearing age must have a negative pregnancy test within 14 days of the first dosing, and if pregnant, Patients are required for ultrasound examination to exclude pregnancy);

8. Women of childbearing age who are not willing to take effective contraception during treatment;

9. There are serious non-malignant tumor comorbidities that may affect long-term follow-up;

10. Patients have family history of endometrial, ovarian or other gynecologic malignancies;

11. Transvaginal ultrasound suggested more serious ovarian abnormalities or endometrial thickening;

12. Patients have had thrombotic events such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis, and pulmonary embolism within 6 months prior to study initiation;

13. Serious liver insufficiency with Child-Pugh C grade;

14. Serious cardiac insufficiency with New York Heart Association (NYHA) grade ≥III;

15. Patients are known severely allergic to study drug;

16. Patients have history of other malignancies in the past five years, except for cutaneous basal cell carcinoma and cervical carcinoma in situ which have been cured;

17. In other cases, the researchers don't think the subjects are suitable for participate in the study.