Efficacy and Safety of Rapamycin (Sirolimus) in the Treatment of Symptomatic Uterine Fibroids and Leiomyomatosis

A prospective non-randomized open label clinical trial to research the efficacy and safety of sirolimus in patients with symptomatic, recurrent uterine fibroids or/and various rare leiomyoma.

Study Overview

• Status: Recruiting
• Conditions: Uterine Fibroids
• Intervention / Treatment: Drug: rapamycin

Detailed Description

Recent studies indicate that mTOR pathway is a specific and sensitive tumor target molecule in uterine fibroids, which can be used as a target molecule for interventional therapy and can provide a new cut-in point for nonoperative treatment. However, the application of mTOR inhibitor (sirolimus) in the treatment of uterine fibroids remains blank. Our study was designed as a prospective non-randomized open label clinical trial to research its efficacy and safety.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fengzh Feng, MD; Phone Number: +86 18612671869; Email: fengfzh@pumch.cn
• Study Contact Backup: Name: Lan Zhu, MD; Email: zhu_julie@sina.com

Study Locations

• China
  • China/Beiing
    • Beijing, China/Beiing, China, 100000
      • Recruiting
      • Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences
      • Contact: Fengzh Feng, MD; Phone Number: +86 18612671869; Email: fengfzh@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria

1. Patients who suffer from menorrhagia and pressure symptoms and whose pelvic ultrasound or pelvic MRI indicates uterine fibroids; or who has underwent myomectomy but suffer from menorrhagia and pressure symptoms again with pelvic ultrasound or pelvic MRI indicating uterine fibroids; or whose other imageological examinations or established surgical diagnosis indicate various rare types of myomatosis and who expect a drug therapy.

2. Symptoms of uterine fibroids can be confirmed if one or multiple symptoms below exist:

   • MP shows an excessive amount of bleeding during menstruation (>80.0 mL)
   • A subject report shows three excessive amounts of bleeding during menstruation in latest six months
   • A subject report indicates pelvic pressure symptoms/pain that are likely related to uterine fibroids.
3. According to results of medical history, physical examinations, gynecological examinations and laboratory examinations, patients are in a good overall condition (except uterine fibroids).
4. Cervical smears show a normal result or have no clinical significance, where further follow-up is unnecessary. If there's a normal result in the latest six month in the medical record of a subject, the subject can pass the inspection of cervical smears. A HPV test can be applied to subjects with equivocal ASCUS as an auxiliary test. ASCUS subjects who get a negative result of a HPV test can be included into this study.
5. Endometrial biopsy should be conducted to eliminate non-endometrial lesions if necessary.
6. Subjects didn't receive any drug therapy for uterine fibroids three months before the clinical test.
7. Female adults have menstruation (>18 years old) and are not during pregnancy and lactation.

8. Subjects have good organ function and results of their biochemical examinations meet the following conditions:

   • AST≤2.5×the upper limit of normal (ULN),
   • ALT≤2.5×the upper limit of normal (ULN),
   • Serum total bilirubin≤1.5×the upper limit of normal (ULN),
   • Creatinine≤1.5×the upper limit of normal (ULN).
9. Patients have signed the informed consent.

Exclusion Criteria

1. Patients are in a period of pregnancy and lactation (patients delivered, miscarried or breast-feed in three months before the treatment)
2. Patients are allergic to any ingredient of the medicine
3. Patients suffer from a disease requiring immediate blood transfusion

4. Patients suffer from a disease that may impact implementation of the study or explanation of results. This type of diseases includes:

   • Known severe blood coagulation disorders
   • Known anemia that is not caused by HMB
   • Known hemoglobinopathy
   • Patients suffered or suffer from cancer of the uterus, cervical carcinoma, ovarian cancer or breast cancer 5) An ultrasonic examination shows one or multiple ovarian cysts with a diameter >30 mm 6) Ovarian tumors or pelvic mass of unknown origin 7) Known or suspected endometrial polyp >15 mm
5. Alcohol or drug (such as aperient) abuse
6. Undiagnosed abnormal bleeding of the reproductive system.
7. Patients also participate in another clinical medicine study
8. Patients took part in another clinical trial that may influence this study before this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rapamycin; rapamycin, 2 mg a day, orally ,for 3months	Drug: rapamycin; rapamycin, 2 mg a day, orally ,for 3months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
size of uterus and the myoma	efficacy assessment	2 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hormone levels	ovarian function assessment	2 day
menstrual blood volume / haemorrhage	symptom assessment	1 day
adverse event	safety assessment	2 day
follicular size	safety assessment	2 day

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Fritsch M, Schmidt N, Groticke I, Frisk AL, Keator CS, Koch M, Slayden OD. Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease. PLoS One. 2015 Nov 20;10(11):e0142429. doi: 10.1371/journal.pone.0142429. eCollection 2015.
• Prizant H, Sen A, Light A, Cho SN, DeMayo FJ, Lydon JP, Hammes SR. Uterine-specific loss of Tsc2 leads to myometrial tumors in both the uterus and lungs. Mol Endocrinol. 2013 Sep;27(9):1403-14. doi: 10.1210/me.2013-1059. Epub 2013 Jul 2.
• Kashani BN, Centini G, Morelli SS, Weiss G, Petraglia F. Role of Medical Management for Uterine Leiomyomas. Best Pract Res Clin Obstet Gynaecol. 2016 Jul;34:85-103. doi: 10.1016/j.bpobgyn.2015.11.016. Epub 2015 Nov 25.
• Suo G, Sadarangani A, Tang W, Cowan BD, Wang JY. Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells. Reprod Sci. 2014 Sep;21(9):1161-70. doi: 10.1177/1933719114532839. Epub 2014 Apr 30.
• Prizant H, Hammes SR. Minireview: Lymphangioleiomyomatosis (LAM): The "Other" Steroid-Sensitive Cancer. Endocrinology. 2016 Sep;157(9):3374-83. doi: 10.1210/en.2016-1395. Epub 2016 Jul 13.

Helpful Links

• Xenograft Model for Predicative Study of Uterine Fibroid Disease
• Uterine-Specific Loss of Tsc2 Leads to Myometrial Tumors in Both the Uterus and Lungs
• Medical Management for Uterine Leiomyomas
• Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells
• Lymphangioleiomyomatosis (LAM)

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: March 10, 2018
• First Submitted That Met QC Criteria: April 14, 2018
• First Posted (Actual): April 18, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2018
• Last Update Submitted That Met QC Criteria: April 14, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Treatment; Complications; mammilian target of rapamycin inhibitor; Rapamycin (sirolimus)
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Leiomyoma; Myofibroma; Leiomyomatosis; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: LPMS201802

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Network platform, and the website will be attached later
• IPD Sharing Time Frame: Within twelve months after the trial complete
• IPD Sharing Access Criteria: Data access requests will be reviewed by an external independent review panel. Requestors will be required to sign a Data Access Agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No