Fibroid, Fibroid Uterus, Leiomyoma, Leiomyoma, Uterine
Conditions
Brief summary
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
DRUGLetrozole 2.5mg
Oral letrozole 2.5mg/day
OTHERPlacebo
Placebo capsule
Sponsors
University of California, San Francisco
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 53 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Uterine leiomyoma-related symptom severity over 12 weeks of treatment | Baseline to 12 weeks | Change in Uterine Fibroid Symptoms Quality of Life (UFS-QOL) Symptom Severity Scale (SSS) score \[Range 8-40 with higher score indicating worse symptoms and worse outcomes\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Uterine leiomyoma-related quality of life over 12 weeks of treatment | Baseline to 12 weeks | Change in Uterine Fibroid Symptoms Quality of Life (UFS-QOL) Health-Related QOL component score \[Range 29-145 points, with higher score indicating better QoL and better outcomes\] |
| Total leiomyoma volume over 12 weeks of treatment | Baseline to 12 weeks | Change in total leiomyoma volume based on pelvic ultrasound measurements |
| Total uterine volume over 12 weeks of treatment | Baseline to 12 weeks | Change in total uterine volume based on pelvic ultrasound measurements |
| Symptoms of heavy menstrual bleeding | Baseline to 12 weeks | Change in symptoms of heavy menstrual bleeding based on a modified Menstrual Bleeding Questionnaire (MBQ) score \[Range 0-48 with higher MBQ score indicating worse symptoms and a negative impact on quality of life\] |
| Improvement in Sexual Functioning | Baseline to 12 weeks | Change in pelvic problems-related sexual function as measured by the Sexual Health Outcomes in Women Questionnaire (SHOW-Q) Pelvic Problems Interference subscale score \[Range 0-100 with higher scores indicating better sexual function\] |
| Symptoms of pelvic pain | Baseline to 12 weeks | Change in pelvic pain severity/intensity "on average" (evaluated on a standard numerical rating scale of 0-10, lower rating indicating better outcomes and less pain) |
| Symptoms of urogenital distress | Baseline to 12 weeks | Change in distressing urogenital symptoms such as urinary frequency, urinary incontinence, and genital pain, as measured by Urogenital Distress Inventory-6 (UDI-6) \[Range 0-100 with higher scores indicating higher disability/worse outcomes\] |
| Effect of letrozole on serum cholesterol levels | Baseline to 12 weeks | Change in serum LDL cholesterol levels |
| Effect of letrozole on serum estradiol levels | Baseline to 12 weeks | Change in serum estradiol levels |
| Effect of letrozole on frequency of hot flashes | Baseline to 12 weeks | Change in frequency of vasomotor symptoms (hot flashes) as measured by the Hot Flush Rating Scale (HFRS) \[no scale range but less # of reported hot flashes indicates better outcome\] |
Countries
United States
Contacts
CONTACTStudy Coordinator
CONTACTLisa Abinanti
PRINCIPAL_INVESTIGATORVanessa Jacoby, MD, MAS
University of California, San Francisco
PRINCIPAL_INVESTIGATORAlison Huang, MD, MAS
University of California, San Francisco
Outcome results
None listed