Prescription of Letrozole for Uterine Myoma

Official title

Letrozole for Treatment of Uterine Fibroids: A Randomized, Placebo-Controlled Trial

Overview

The PLUM Study is a randomized, double-blinded, 2-arm, parallel-group, placebo-controlled trial is designed to compare the efficacy of letrozole versus placebo on leiomyoma-related symptoms and quality of life as well as leiomyoma and uterine size.

Interventions

• Drug Letrozole 2.5mg
  Oral letrozole 2.5mg/day
• Other Placebo
  Placebo capsule

Primary outcome measures

• Uterine leiomyoma-related symptom severity over 12 weeks of treatment [Time frame: Baseline to 12 weeks]

Secondary outcome measures (10)

• Uterine leiomyoma-related quality of life over 12 weeks of treatment [Time frame: Baseline to 12 weeks]
• Total leiomyoma volume over 12 weeks of treatment [Time frame: Baseline to 12 weeks]
• Total uterine volume over 12 weeks of treatment [Time frame: Baseline to 12 weeks]
• Symptoms of heavy menstrual bleeding [Time frame: Baseline to 12 weeks]
• Improvement in Sexual Functioning [Time frame: Baseline to 12 weeks]
• Symptoms of pelvic pain [Time frame: Baseline to 12 weeks]
• Symptoms of urogenital distress [Time frame: Baseline to 12 weeks]
• Effect of letrozole on serum cholesterol levels [Time frame: Baseline to 12 weeks]
• Effect of letrozole on serum estradiol levels [Time frame: Baseline to 12 weeks]
• Effect of letrozole on frequency of hot flashes [Time frame: Baseline to 12 weeks]

Eligibility criteria

Inclusion criteria

• At least 21 and less than 54 years of age (to focus on an adult, premenopausal population)
• Female sex, based on sex identified on their birth certificate (no other gender requirements)
• Have uterine leiomyomata that have been visualized on pelvic imaging (i.e., ultrasound or MRI) in the last 24 months
• Report symptoms associated with leiomyomata such as heavy uterine bleeding, pelvic pressure or discomfort, urinary or bowel abnormalities, or dyspareunia for the past 3 months
• Have at least moderate leiomyomata symptom burden, with UFS-QOL SSS score of 30 or higher at baseline
• Has had a menstrual period in the past 3 months (90 days)
• Agree to use a non-hormonal or barrier method of contraception with any sexual activity with a non-sterile male partner during the study period (i.e., use of copper IUD is consistent with eligibility)

Exclusion criteria

• Screening pelvic imaging indicating any leiomyomata ≥10 cm in maximum diameter, or uterine size ≥16 cm in length (equivalent to 16 weeks gestation)-note that candidates who exclusively have prior clinical pelvic imaging 12-24 months ago will be excluded if imaging includes leiomyomata ≥9 cm in maximum diameter, or uterine size ≥15 cm in length, presuming leiomyoma growth of ≥1 cm per year
• Screening pelvic imaging indicating only one, sole leiomyoma <2 cm in maximum diameter
• Any submucosal leiomyoma that is >50% within uterine cavity (FIGO Type 0 or Type 1 leiomyomata)
• Visit to the emergency room or hospitalization for leiomyoma symptoms in the last 12 weeks
• Leiomyomata treated by surgery, radiologic procedure in the last 12 weeks; or plans to undergo any of the above in the next 24 weeks
• Leiomyomata treated by GRNH agonist or antagonist in the last 12 weeks (if injected) or in the last 4 weeks (if oral); or plans to use the above in the next 24 weeks
• Currently pregnant or lactating, pregnant or lactating in the past 12 weeks, or planning to become pregnant in the next 24 weeks
• Screening serum hemoglobin <8 g/dL, or history of blood transfusion in the last 12 weeks (indicating severe anemia)
• Screening cholesterol lipid panel testing showing LDL cholesterol level ≥ 190 mg/dL (due to rare side effects over long-term use of aromatase inhibitors in postmenopausal women)
• Screening serum estradiol level <30 pg/mL (consistent with postmenopausal status)
• For women aged 45 years or older only: irregular menstrual cycles (menstrual cycles <21 days or >38 days between periods), prolonged menstrual bleeding (bleeding >14 days), or bleeding in between menstrual periods, unless already evaluated by a clinician to discuss endometrial biopsy (uterine biopsy) to rule out endometrial hyperplasia.
• History of osteoporosis (based on self-reported DEXA indicating bone mineral density Z-score < -2.0 at spine, total hip, or femoral neck; a prior fracture judged to be a fragility fracture; or self-reported use of bisphosphonates, calcitonin, calcitriol, ipriflavone, teriparatide, or denosumab for bone density loss)
• History of severe liver disease (Child Pugh Class C cirrhosis), posing safety risks for use of letrozole
• Current or prior history of breast cancer (given potential need to take letrozole for breast cancer treatment or secondary prevention)
• Screening pelvic imaging indicating an Ovarian-Adnexal Reporting and Data System (O-RADS) category 3, 4, or 5 ovarian or adnexal lesion
• Screening pelvic imaging concerning for other current cancer of the gynecologic, genitourinary or gastrointestinal system
• Prior hypersensitivity or significant adverse reaction to letrozole or any aromatase inhibitor, or to an ingredient in the placebo capsule
• Use of letrozole, other aromatase inhibitor, or selective estrogen receptor modulator (SERM) medications in the past 4 weeks, or existing plans to initiate one of these in the next 24 weeks
• Use of oral, vaginal, or topical exogenous estrogen, progestin, or androgen therapy in the past 4 weeks; or injectable forms of the above in the past 12 weeks; or plans to initiate any of the above in the next 24 weeks
• Use of medications with potential unsafe interactions with letrozole in the past 4 weeks (methadone, levomethadone, nintedanib, thalidomide), or plans to initiate these in the next 24 weeks
• Any condition that, in the opinion of the investigators, would interfere with ability to complete study procedures, including acute or uncontrolled mental health condition, substance abuse, or inability to complete procedures in English (or Spanish, for sites that offer study assessments in Spanish)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 5 centers

• University of California, Los Angeles — Los Angeles
• University of California, San Francisco — San Francisco
• Mayo Clinic — Rochester
• University of Mississippi Medical Center — Jackson
• Duke University — Durham

Identifiers

NCT: NCT06143631 · 23-39255 · R01HD112465

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗