External Mastalgia-oil Versus Oral Tamoxifen in Premenopausal Women with Severe Mastalgia

External Mastalgia-oil Versus Oral Tamoxifen in Premenopausal Women with Severe Mastalgia: a Double-blind, Double-simulated, Positive-controlled Randomized Clinical Trial

This is a single-center, double-blind, double-simulated, positive-controlled, randomized clinical trial to explore the efficacy and safety of external mastalgia-oil versus oral tamoxifen in premenopausal women with severe mastalgia.

Study Overview

• Status: Not yet recruiting
• Conditions: Mastalgia
• Intervention / Treatment: Drug: mastalgia-oil, tamoxifen placebo; Drug: mastalgia-oil placebo, tamoxifen

• Study Type: Interventional
• Enrollment (Estimated): 456
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chang Gong, Prof; Phone Number: 02034070499; Email: gchang@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-sen Memorial Hospital of Sun Yat-sen University
      • Contact: Gong Chang, Prof; Phone Number: 02034070499; Email: gchang@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Premenopausal females aged ≥ 18 years old
• Pre-existing regular menstrual cycle (28 ± 3 days) with mastalgia lasting for at least 6 consecutive menstrual cycles; with severe mastalgia [visual analog scale (VAS) score ≥ 4 for at least 7 days] and without chest wall pain in the baseline menstrual cycle (nonmedicated menstrual cycle)
• With breast ultrasound: BI-RADS classification 1-3; if mammography is required: also BI-RADS classification 1-3
• Willingness to follow up and complete required tests; ability to complete questionnaires independently or with assistance
• Willingness to use effective contraception (vaginally administered estrogen and hormone-coated IUDs are permitted) prior to study entry, during study participation, and for three months after discontinuation of the drug; negative pregnancy test in females of childbearing potential
• Requisite laboratory values:white blood cell count: ≥ 4.0 × 10^9/L, absolute neutrophil count: ≥ 2 × 10^9/L, platelet count: ≥ 100 × 10^9/L; hemoglobin: ≥ 110 g/L; aspartate aminotransferase and alanine aminotransferase: ≤ upper limit of normal, alkaline phosphatase: ≤ upper limit of normal, blood total bilirubin: ≤ upper limit of normal; serum creatinine and blood urea nitrogen: ≤ upper limit of normal

Exclusion Criteria:

• With suspected breast disease (e.g., mastitis, malignant breast tumor) other than breast pain or benign breast cysts, or with other malignant tumors
• Use of hormonal medications (e.g., oral contraceptives, glucocorticoids, etc.), sex hormone modulators (SERMS, AIs, SERDs, etc.), B vitamins, essential oils, nonsteroidal anti-inflammatory drugs, or higher pain relievers in the past 3 months; use of tamoxifen or analogs in the past 6 months
• Prior history of breast surgery (including minimally invasive surgery), history of malignancy, or history of thromboembolism within the last 5 years (history of varicose veins and superficial phlebitis allowed)
• Smokers; tamoxifen or essential oils systemic/skin sensitization
• With serious primary diseases of the heart, liver, kidneys and hematopoietic system, or mental illness, etc.
• Accompanied by skin damage on the breast that destroys the stratum corneum (e.g., eczema, ulcers)
• Serious or uncontrolled infections that may interfere with study treatment or assessment of study results, including but not limited to active hepatitis viral infection, human immunodeficiency virus antibody positivity, syphilis spirochete antibody positivity with evidence of active infection, and pulmonary infections
• Subjects who are breastfeeding or pregnant at the time of screening (of childbearing age and with serum human chorionic gonadotropin test results higher than the reference value); subjects of childbearing age who have had unprotected sex with a heterosexual partner within 2 weeks prior to the screening; subjects of childbearing age who are planning to prepare for conception, become pregnant, breastfeed, or donate their eggs during the test period or within 3 months of the end of the test; and those with implanted breasts
• Decrease in total breast pain score by more than 25% during the placebo lead-in cycle. These patients will not receive subsequent randomization and treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: external mastalgia-oil plus oral tamoxifen placebo	Drug: mastalgia-oil, tamoxifen placebo; external mastalgia-oil 1 ml/d per breast plus oral tamoxifen placebo 10mg/d for 3 consecutive menstrual cycles
Active Comparator: oral tamoxifen plus external mastalgia-oil placebo	Drug: mastalgia-oil placebo, tamoxifen; oral tamoxifen 10mg/d plus external mastalgia-oil placebo 1 ml/d per breast for 3 consecutive menstrual cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mastalgia clinical response rate	The recruited patients with mastalgia will be asked to record their symptoms of breast pain using a daily VAS breast pain chart, and the sum of the daily VAS within a menstrual cycle is considered the breast pain score (BPS). Effective rate (%)= [BPS (P) - BPS (T3)]/BPS (P)*100%, where BPS (P) indicates BPS of the placebo lead-in cycle and BPS (T3) indicates BPS at the end of the third treatment cycle. An effective rate of more than 50% is considered a clinical response.	Within 4 weeks after the end of the third treatment menstrual cycle
Safety (adverse events)	Total incidence of the following adverse events: hot flashes + leukorrhea + menorrhagia + nausea + headache + skin reactions. Adverse events will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).Each patient will be counted only once for the above adverse events experienced.	from signing the informed consent form until 4 weeks after the end of the third treatment menstrual cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subgroup mastalgia clinical response rate	Mastalgia clinical response rate in women with cyclical mastalgia; Mastalgia clinical response rate in women with non-cyclical mastalgia	Within 4 weeks after the end of the third treatment menstrual cycle
Breast nodularity	Breast nodularity will be assessed according to the Lucknow-Cardiff breast nodularity scale.The above breast nodularity scale is a 5-point ordinal scale depicting increasing order of nodularity in upper outer quadrants of the breasts. Grade-0 depicts a smooth textured breast with extreme extent of normalcy and grade-4 the maximum nodularity.	Within 7 days before the first treatment and the end of each treatment menstrual cycle
Pharmacokinetics of mastodynia-oil	Collection of blood samples for pharmacokinetic trough concentration-effect analysis of mastodynia-oil	Within 4 weeks after the end of the third treatment menstrual cycle
Changes in blood biochemical indicators	Tamoxifen-specific indicators: estradiol, progesterone, et al. and their correlation with the primary endpoints were detected in blood before and after treatment using ELISA.	Within 4 weeks after the end of the third treatment menstrual cycle
Changes in blood metabolites	Comparison of changes in blood metabolites before and after treatment and their correlation with primary endpoints using metabolomics.	Within 4 weeks after the end of the third treatment menstrual cycle

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Chang Gong, Prof, Breast Tumor Center, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Publications and helpful links

General Publications

• Kumar S, Rai R, Das V, Kumar S, Dwivedi V, Agrawal GG. Visual analogue scale for assessing breast nodularity in non-discrete lumpy breasts: the Lucknow-Cardiff breast nodularity scale. Breast. 2010 Jun;19(3):238-42. doi: 10.1016/j.breast.2010.02.002. Epub 2010 Mar 11.

Study record dates

Study Major Dates

• Study Start (Estimated): January 16, 2025
• Primary Completion (Estimated): January 16, 2029
• Study Completion (Estimated): May 16, 2030

Study Registration Dates

• First Submitted: April 26, 2024
• First Submitted That Met QC Criteria: May 5, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): November 29, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Mastodynia; Antineoplastic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Hormone Antagonists; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: SYSKY-2024-292-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No