Prescription of Letrozole for Uterine Myoma

Study Overview
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Brief Summary
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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.

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

Conditions
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Leiomyoma, Uterine, Leiomyoma, Fibroid, Fibroid Uterus

Intervention / Treatment
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* Drug: Letrozole 2.5mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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, dyspareunia, with UFS-QOL SSS score of at least 30 at baseline) Has regularly-occurring menstrual periods of ≤ 14 days duration with a cycle of 21 to 38 days from the start of one menstrual period until the start of the next, by patient history for at least 3 months prior to screening Agree to use a non-hormonal barrier method of contraception during the study period if at risk for pregnancy (any sexual activity with a non-sterile male partner) Exclusion Criteria: Screening pelvic imaging indicating any leiomyomata ≥8 cm in maximum diameter, or uterine size ≥14 cm in length (equivalent to 14 weeks gestation)-note that candidates with prior clinical pelvic imaging 12-24 months ago will be excluded if imaging includes leiomyomata ≥7 cm in maximum diameter, or uterine size ≥13 cm in length, presuming leiomyoma growth of ≥1 cm per year 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; or plans to use the above in the next 24 weeks Any submucosal leiomyoma >1cm that is >50% within uterine cavity (FIGO Type 0 or Type 1 leiomyomata) amenable to hysteroscopic resection Currently pregnant or lactating, pregnant or lactating in the past 12 weeks, or planning to become pregnant in the next 24 weeks Hemoglobin <8 g/dL or required blood transfusion in the last 12 weeks Visit to the emergency room or hospitalization for leiomyoma symptoms in the last 12 weeks Age ≥45 years with irregularly timed, heavy bleeding that has not yet been evaluated by endometrial biopsy, or endometrial biopsy indicating hyperplasia or malignancy History of osteoporosis (based on self-reported DEXA indicating bone mineral density Z-score < -2.0 at spine, total hip, or femoral neck, or based on a fracture judged to be a fragility fracture) or self-reported history of the use of bisphosphonates, calcitonin, calcitriol, ipriflavone, teriparatide, denosumab, or any medication other than calcium and vitamin D preparations to treat bone mineral density loss Serum LDL cholesterol >160 mg/dL (due to rare side effects over long-term use of aromatase inhibitors reported in postmenopausal women with breast cancer) History of severe liver disease (Child Pugh Class C cirrhosis) Current or prior history of breast cancer Pelvic imaging concerning for 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 plans to initiate in the next 24 weeks Use of exogenous estrogen, progestin, or androgen therapy in the past 4 weeks, or plans to initiate 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 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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 54 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole<br>Oral letrozole 2.5mg/day | Drug: Letrozole 2.5mg<br>* Oral letrozole 2.5mg/day<br>|
| Placebo Comparator: Placebo and Letrozole<br>Placebo capsule for 12 weeks; Oral letrozole 2.5mg/day for 12 weeks | Other: Placebo<br>* Placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fibroid symptom severity | Change in UFS-Qol Symptom Severity Score from Baseline to 12 Weeks. | Baseline to 12 weeks | 
| Change in fibroid symptom severity | Change in UFS-Qol Symptom Severity Score from Baseline to 24 Weeks. | Baseline to 24 weeks |