PLUM: Pilot of Letrozole for Uterine Myomas

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT02470741
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 29
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

PLUM evaluates the drug letrozole as a treatment for uterine fibroids. This study is a randomized, blinded, placebo-controlled trial of oral letrozole among premenopausal women with symptomatic uterine fibroids. Participants will be randomly assigned in a 1:1 ratio to either oral letrozole 2.5mg/day for 6 months (Group A) or intermittent dosing with letrozole 2.5mg/day and an identical placebo capsule (Group B).

Condition or Disease	Intervention/Treatment	Phase
Leiomyoma; Uterine Fibroids	Drug: Letrozole; Other: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Pilot of Letrozole for Uterine Myomas
• Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Letrozole Oral letrozole 2.5mg/day	Drug: Letrozole; Other Names: Femara
Placebo Comparator: Placebo and Letrozole Intermittent oral letrozole 2.5mg/day for 2 months and an identical placebo capsule for 4 months	Drug: Letrozole; Other Names: Femara ; Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Changes in Fibroid-related Symptoms After Treatment With Letrozole [Baseline to 2 Months]

   The Uterine Fibroid Sympton and Quality of Life (UFS-QoL) Symptom Severity score measures self-reported severity of fibroid-related symptoms. Symptoms include: fatigue, sleep, self-image, mood disturbances/psychologic distress, fear of embarrassment, interference with daily activities, relationships with family and friends, and sexual functioning. Scores range from 0 to 100; higher scores indicate greater symptom severity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. ≥21 years old

2. Premenopausal (at least one menses in last 3 months)

3. Symptomatic fibroids (fibroids visualized on ultrasound or MRI and heavy uterine bleeding, pelvic pressure or discomfort, urinary or bowel abnormalities, dyspareunia)

4. Fibroids that are ≤4 in total number or Fibroids that are ≤7 in total number if all fibroids are less than 4cm (40 mm) each

5. Fibroids that are ≤7cm in maximum diameter, on screening imaging, if ≤4 fibroids in total number(fibroid is defined as any mass with radiographic characteristics of fibroid >2cm)

6. Up to date in Pap smear screening and surveillance

7. Endometrial biopsy (required if age>45 years with irregular bleeding) does not indicate premalignant or malignant cells

8. Agree to use non-hormonal barrier method of contraception during study period if at risk for pregnancy

9. Has primary care provider or gynecologist

10. Agrees not to start new medications/treatments for fibroids during the study

11. Able to give informed consent

Exclusion Criteria:

1. Fibroids treated by surgery, radiologic procedure, or GnRH agonist or antagonist in the last 3 months

2. Any submucosal fibroid ≥2cm that is >50% in uterine cavity (FIGO Type 0 or Type 1 fibroids) amenable to hysteroscopic resection

3. Use of exogenous estrogen and/or progestin in the last month. (for 3 month long-acting depoprovera injection, no use in last 3 months)

4. Pregnant, lactating, or planning to become pregnant in the next 6 months

5. Hematocrit <27% or visit to emergency room or hospitalization for fibroid symptoms in the last 3 months (cannot be safely randomized to a placebo)

6. History of osteopenia or osteoporosis

7. History of hyperlipidemia

8. Current liver or kidney disease

9. Unable or unwilling to attend 4 study visits

10. Pelvic imaging concerning for gynecologic cancer or cancer of the genitourinary or gastrointestinal system

11. Does not have primary care provider or gynecologist

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94158

Sponsors and Collaborators

• University of California, San Francisco

Investigators

• Principal Investigator: Vanessa Jacoby, MD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 19, 2015

More Information

Additional Information:

• Fibroid Trials at UCSF

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02470741
• Other Study ID Numbers: 15-15678
• First Posted: Jun 12, 2015
• Last Update Posted: Nov 15, 2019
• Last Verified: Nov 1, 2019

• Additional relevant MeSH terms: Leiomyoma; Myofibroma; Letrozole

Study Results

Participant Flow

Arm/Group Title	Letrozole	Placebo and Letrozole
Arm/Group Description	Oral letrozole 2.5mg/day	Intermittent oral letrozole 2.5mg/day for 2 months and an identical placebo capsule for 4 months
Period Title: Overall Study
STARTED	6	6
COMPLETED	3	4
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Letrozole	Placebo and Letrozole	Total
Arm/Group Description	Oral letrozole 2.5mg/day	Intermittent oral letrozole 2.5mg/day for 2 months and an identical placebo capsule for 4 months	Total of all reporting groups
Overall Participants	6	6	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.33 (4.2)	39.50 (7.4)	42.92 (6.8)
Sex: Female, Male (Count of Participants)
Female	6 100%	6 100%	12 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White or Caucasian	2 33.3%	2 33.3%	4 33.3%
Black or African American	0 0%	2 33.3%	2 16.7%
Hispanic or Latina	0 0%	0 0%	0 0%
Asian	1 16.7%	1 16.7%	2 16.7%
Native Hawaiian or other Pacific Islander	0 0%	0 0%	0 0%
American Indian/Alaska Native	0 0%	0 0%	0 0%
Other	1 16.7%	1 16.7%	2 16.7%
More than one race reported	2 33.3%	0 0%	2 16.7%
UFS-QOL Symptom Severity Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	53.65 (25.00)	42.71 (9.0)	48.18 (18.8)

Outcome Measures

1. Primary Outcome

Title	Changes in Fibroid-related Symptoms After Treatment With Letrozole
Description	The Uterine Fibroid Sympton and Quality of Life (UFS-QoL) Symptom Severity score measures self-reported severity of fibroid-related symptoms. Symptoms include: fatigue, sleep, self-image, mood disturbances/psychologic distress, fear of embarrassment, interference with daily activities, relationships with family and friends, and sexual functioning. Scores range from 0 to 100; higher scores indicate greater symptom severity.
Time Frame	Baseline to 2 Months

Outcome Measure Data

Analysis Population Description

The final analysis excludes one participant in the placebo/letrozole group who dropped out of the study after baseline but prior to starting study medication and the Month 2 visit.

Arm/Group Title	Letrozole	Placebo and Letrozole
Arm/Group Description	Oral letrozole 2.5mg/day	Intermittent oral letrozole 2.5mg/day for 2 months and an identical placebo capsule for 4 months
Measure Participants	6	5
Least Squares Mean (95% Confidence Interval) [units on a scale]	-10.42	1.43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Letrozole, Placebo and Letrozole
	Comments	Null hypotheses: Letrozole is not associated with an improvement in the UFSQOL Overall Score.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	Mixed Models Analysis
	Comments	Repeated measures mixed models, with unstructured co-variance matrix.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-11.85
	Confidence Interval	(2-Sided) 95%; -32.92 to 9.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model generated LS Mean Differences

Adverse Events

Time Frame	7 months. Adverse Events were collected beginning at Baseline until 1 month after study completion.
Arm/Group Title	Letrozole		Placebo and Letrozole
Arm/Group Description	Oral letrozole 2.5mg/day		Intermittent oral letrozole 2.5mg/day for 2 months and an identical placebo capsule for 4 months
All Cause Mortality
	Letrozole		Placebo and Letrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Letrozole		Placebo and Letrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Letrozole		Placebo and Letrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		3/6 (50%)
Gastrointestinal disorders
Stomach aches	0/6 (0%)	0	1/6 (16.7%)	1
General disorders
Dizziness/Light-headedness	1/6 (16.7%)	1	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle or joint pain/strain	0/6 (0%)	0	1/6 (16.7%)	1
Psychiatric disorders
Irritable	0/6 (0%)	0	1/6 (16.7%)	1
Renal and urinary disorders
Pelvic pressure increasing urination	1/6 (16.7%)	1	0/6 (0%)	0
Reproductive system and breast disorders
Bleeding between periods	1/6 (16.7%)	1	0/6 (0%)	0
Pain in uterus	0/6 (0%)	0	1/6 (16.7%)	1
Cyst	0/6 (0%)	0	1/6 (16.7%)	1
Skin and subcutaneous tissue disorders
Oily skin	0/6 (0%)	0	1/6 (16.7%)	1
Vascular disorders
Hot flashes/night sweats	0/6 (0%)	0	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.