Comparing Tamoxifen and Toremifene for Early Breast Cancer in Certain Patients

Multicenter Prospective, Parallel-controlled Phase III Clinical Study on Comparing Efficacy of Tamoxifen Versus Toremifene in CYP2D6 Intermediate/Poor Metabolizers of Premenopausal Patients With ER-positive Early Breast Cancer

This study is testing whether tamoxifen or toremifene works better for premenopausal women with early breast cancer who have certain genetic traits that affect how they process these medications.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 844 (estimated)
• Ages: 18 Years to 50 Years
• Sex: Female
• Sponsor: Chinese Anti-Cancer Association (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 21 sites (Beijing, Beijing and 20 other locations)
• Trial ID: NCT03351062 on ClinicalTrials.gov

What this trial studies

This clinical trial is a multi-center, prospective, parallel-controlled Phase III study aimed at comparing the efficacy of tamoxifen and toremifene in premenopausal women with estrogen receptor-positive early breast cancer who are CYP2D6 intermediate or poor metabolizers. The study focuses on the 5-year disease-free survival rate and overall survival of participants receiving these two selective estrogen receptor modulators (SERMs). Given that CYP2D6 variant carriers may not benefit from tamoxifen, the trial seeks to provide insights into more effective treatment options for this population. Participants will undergo genotype screening to confirm their eligibility based on CYP2D6 polymorphisms.

Who should consider this trial

Good fit: Ideal candidates for this study are premenopausal women aged 18-50 years with estrogen receptor-positive early breast cancer who are identified as CYP2D6 intermediate or poor metabolizers.

Not a fit: Patients who are not CYP2D6 variant carriers or those with advanced breast cancer may not receive benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more effective treatment options for premenopausal women with early breast cancer who are CYP2D6 variant carriers.

How similar studies have performed: Previous studies have indicated that toremifene may be more effective than tamoxifen for CYP2D6 variant carriers, suggesting potential success for this comparative approach.

Eligibility 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.

Where this trial is running

Beijing, Beijing and 20 other locations

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences — Beijing, Beijing, China (Recruiting)
• First Affiliated Hospital of Chongqing Medical University — Chongqing, Chongqing, China (Recruiting)
• Southwest Hospital, China — Chongqing, Chongqing, China (Recruiting)
• Union hospital of Fujian Medical University — Fuzhou, Fujian, China (Recruiting)
• Guangdong Provincial People's Hospital — Guangzhou, Guangdong, China (Recruiting)
• Sun Yat-sen Memorial Hospital — Guangzhou, Guangdong, China (Recruiting)
• Hainan People's Hospital — Haikou, Hainan, China (Recruiting)
• Hebei Tumor Hospital — Shijiazhuang, Hebei, China (Recruiting)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (Recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Recruiting)
• Wuhan Tongji Hospital — Wuhan, Hubei, China (Recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)
• Jiangsu Provincial People's Hospital — Nanjing, Jiangsu, China (Recruiting)
• The Third Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Recruiting)
• First Hospital of Jilin University — Changchun, Jilin, China (Recruiting)
• First Hospital of China Medical University — Shenyang, Lining, China (Recruiting)
• First Affiliated Hospital of Qingdao University — Qingdao, Shandong, China (Recruiting)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai, China (Recruiting)
• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin, China (Recruiting)
• The Third Affiliated Hospital of Kunming Medical College — Kunming, Yunnan, China (Recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Zhimin Shao, Master — Fudan University
• Study coordinator: Zhimin Shao, M. D.

Conditions Breast Cancer Female; premenopausal; early breast cancer; estrogen receptor positive