Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03351062
Recruitment Status : Recruiting
First Posted : November 22, 2017
Last Update Posted : November 22, 2017
Sponsor:
Collaborators:
Fudan University
Henan Cancer Hospital
The First Hospital of Jilin University
Southwest Hospital, China
First Hospital of China Medical University
Guangdong Provincial People's Hospital
Harbin Medical University
First Affiliated Hospital of Chongqing Medical University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Jiangsu Provincial People's Hospital
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Zhejiang Cancer Hospital
Tianjin Medical University Cancer Institute and Hospital
Union hospital of Fujian Medical University
Hebei Tumor Hospital
Hunan Cancer Hospital
Affiliated Hospital of Qinghai University
Wuhan TongJi Hospital
Hainan People's Hospital
The Third Affiliated Hospital of Kunming Medical College.
The Third Affiliated Hospital of Nanchang University
Information provided by (Responsible Party):
Chinese Anti-Cancer Association

Brief 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.

Condition or disease Intervention/treatment Phase
Breast Cancer Female Drug: Tamoxifen Drug: Toremifene Phase 3

Detailed Description:

STUDY BACKGROUND Breast cancer is a serious disease that threatens human health and life. Especially in China, the incidence rate is increasing year by year. According to WHO data, the incidence of breast cancer in China in 2020 will reach 214,000. Selective estrogen receptor modulators (SERMs) are a classic form of endocrine therapy for early breast cancers, but not all hormone receptor positive breast cancers benefit from specific SERMs. Numerous studies have shown that CYP2D6 variant carriers (around 50% CYP2D6 variant carriers in Chinese population) will not benefit a lot from tamoxifen, and combined use of CYP2D6 inhibitors will further affect the efficacy of tamoxifen. However, studies on another SERM drug - toremifene have shown that its metabolism and pharmacological effects are not influenced by CYP2D6 genotype or enzyme activity. Therefore, in the principle of individualized medicine, it is necessary to compare the efficacy of using tamoxifen and toremifene in CYP2D6 variant carriers in China so as to provide more guidance for clinical use.

OBJECTIVES:

  1. The main purpose of this study is to compare 5-year disease-free survival rate of adjuvant endocrine therapy with tamoxifen and toremifene in premenopausal women with estrogen receptor-positive early breast cancer who are CYP2D6 intermediate/poor metabolizers.
  2. The secondary purpose of this study includes:

    1. To compare 5-year overall survival (OS) and safety of adjuvant endocrine therapy with tamoxifen and toremifene in premenopausal patients with estrogen receptor-positive early breast cancer who are CYP2D6 intermediate/poor metabolizers.
    2. To compare the changes of plasma concentration of the parent drugs and metabolites of tamoxifen and toremifene in premenopausal patients with estrogen receptor-positive early breast cancer who are CYP2D6 intermediate/poor metabolizers.
    3. To assess the pharmacokinetics of tamoxifen and toremifene in premenopausal patients with estrogen receptor-positive early breast cancer who are CYP2D6 intermediate/poor metabolizers.

OUTLINE:

First, CYP2D6 genotype screening shall be conducted in premenopausal patients with estrogen receptor-positive early breast cancer in order to determine the frequency of different alleles. Then, patients who are CYP2D6 intermediate/poor metabolizers (with *4, *5, *10, *14, *17, *41 alleles) shall be stratified and randomized at the ratio of 1:1 ratio: allele status of CYP2D6 CYP2D6 intermediate/poor metabolizer (Heterozygous or homozygous), lymph node metastasis (with vs. without), prior chemotherapy (with vs. without), and HER2 status (positive vs. negative). Included patients shall be divided into two groups. One group will be given Tamoxifen (10mg Bid) for 5 years and the other group will be given toremifene (60mg qd) for 5 years. Then 5-year disease-free rate and overall survival and safety will be compared between these two groups. At Month 6, pharmacokinetic study on tamoxifen, toremifene and their metabolites will be conducted on patients.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 844 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : November 2017
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Active Comparator: Tamoxifen treatment group
Patients in this group will receive tamoxifen treatment.
Drug: Tamoxifen
Patients will be given 10mg Tamoxifen twice a day.
Other Name: Tamoxifen citrate

Active Comparator: Toremifene treatment group
Patients in this group will receive Toremifene treatment.
Drug: Toremifene
Patients will be given 60mg Toremifene once a day.
Other Name: fareston




Primary Outcome Measures :
  1. Disease-Free Survival [ Time Frame: Within 5 years after randomization ]
    The time period from randomization to local or distant invasive cancer recurrence, contralateral invasive breast cancer, second (non-breast) primary invasive cancer and all-cause death


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Within 5 years after randomization ]
    The time period from randomization to all-cause death

  2. Adverse drug reaction [ Time Frame: Within 5 years after administration ]
    The time period from administration to adverse events (dyslipidemia, endometrial hyperplasia) with confirmed, probably and possibly relevant relationship to trial medicine.

  3. Serum drug concentration [ Time Frame: Within 6 months after administration ]
    Blood level of trial medicines and their metabolites



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03351062


Contacts
Layout table for location contacts
Contact: Zhimin Shao, M. D. 13611709888 zhimingshao@yahoo.com
Contact: Ayong Cao, M. D. 18017317218 caca_163@sina.com

Locations
Show Show 21 study locations
Sponsors and Collaborators
Chinese Anti-Cancer Association
Fudan University
Henan Cancer Hospital
The First Hospital of Jilin University
Southwest Hospital, China
First Hospital of China Medical University
Guangdong Provincial People's Hospital
Harbin Medical University
First Affiliated Hospital of Chongqing Medical University
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Jiangsu Provincial People's Hospital
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Zhejiang Cancer Hospital
Tianjin Medical University Cancer Institute and Hospital
Union hospital of Fujian Medical University
Hebei Tumor Hospital
Hunan Cancer Hospital
Affiliated Hospital of Qinghai University
Wuhan TongJi Hospital
Hainan People's Hospital
The Third Affiliated Hospital of Kunming Medical College.
The Third Affiliated Hospital of Nanchang University
Investigators
Layout table for investigator information
Principal Investigator: Zhimin Shao, Master Fudan University
Layout table for additonal information
Responsible Party: Chinese Anti-Cancer Association
ClinicalTrials.gov Identifier: NCT03351062    
Other Study ID Numbers: CYP2D6-1.1
First Posted: November 22, 2017    Key Record Dates
Last Update Posted: November 22, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Chinese Anti-Cancer Association:
premenopausal
early breast cancer
estrogen receptor positive
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Toremifene
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents