Efficacy and Safety of Rapamycin (Sirolimus) in the Treatment of Symptomatic Uterine Fibroids and Leiomyomatosis
Primary Purpose
Uterine Fibroids
Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
rapamycin
Sponsored by
About this trial
This is an interventional treatment trial for Uterine Fibroids focused on measuring mammilian target of rapamycin inhibitor, Rapamycin (sirolimus), Treatment, Complications
Eligibility Criteria
Inclusion Criteria
- 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.
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.
- According to results of medical history, physical examinations, gynecological examinations and laboratory examinations, patients are in a good overall condition (except uterine fibroids).
- 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.
- Endometrial biopsy should be conducted to eliminate non-endometrial lesions if necessary.
- Subjects didn't receive any drug therapy for uterine fibroids three months before the clinical test.
- Female adults have menstruation (>18 years old) and are not during pregnancy and lactation.
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).
- Patients have signed the informed consent.
Exclusion Criteria
- Patients are in a period of pregnancy and lactation (patients delivered, miscarried or breast-feed in three months before the treatment)
- Patients are allergic to any ingredient of the medicine
- Patients suffer from a disease requiring immediate blood transfusion
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
- Alcohol or drug (such as aperient) abuse
- Undiagnosed abnormal bleeding of the reproductive system.
- Patients also participate in another clinical medicine study
- Patients took part in another clinical trial that may influence this study before this study
Sites / Locations
- Peking Union Medical College Hospital, Chinese Academy of Medicine SciencesRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
rapamycin
Arm Description
rapamycin, 2 mg a day, orally ,for 3months
Outcomes
Primary Outcome Measures
size of uterus and the myoma
efficacy assessment
Secondary Outcome Measures
hormone levels
ovarian function assessment
menstrual blood volume / haemorrhage
symptom assessment
adverse event
safety assessment
follicular size
safety assessment
Full Information
NCT ID
NCT03500367
First Posted
March 10, 2018
Last Updated
April 14, 2018
Sponsor
Peking Union Medical College Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03500367
Brief Title
Efficacy and Safety of Rapamycin (Sirolimus) in the Treatment of Symptomatic Uterine Fibroids and Leiomyomatosis
Official Title
Efficacy and Safety of Rapamycin (Sirolimus) in the Treatment of Symptomatic Uterine Fibroids and Leiomyomatosis
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Unknown status
Study Start Date
January 1, 2018 (Actual)
Primary Completion Date
June 30, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking Union Medical College Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uterine Fibroids
Keywords
mammilian target of rapamycin inhibitor, Rapamycin (sirolimus), Treatment, Complications
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
rapamycin
Arm Type
Experimental
Arm Description
rapamycin, 2 mg a day, orally ,for 3months
Intervention Type
Drug
Intervention Name(s)
rapamycin
Intervention Description
rapamycin, 2 mg a day, orally ,for 3months
Primary Outcome Measure Information:
Title
size of uterus and the myoma
Description
efficacy assessment
Time Frame
2 day
Secondary Outcome Measure Information:
Title
hormone levels
Description
ovarian function assessment
Time Frame
2 day
Title
menstrual blood volume / haemorrhage
Description
symptom assessment
Time Frame
1 day
Title
adverse event
Description
safety assessment
Time Frame
2 day
Title
follicular size
Description
safety assessment
Time Frame
2 day
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
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.
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.
According to results of medical history, physical examinations, gynecological examinations and laboratory examinations, patients are in a good overall condition (except uterine fibroids).
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.
Endometrial biopsy should be conducted to eliminate non-endometrial lesions if necessary.
Subjects didn't receive any drug therapy for uterine fibroids three months before the clinical test.
Female adults have menstruation (>18 years old) and are not during pregnancy and lactation.
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).
Patients have signed the informed consent.
Exclusion Criteria
Patients are in a period of pregnancy and lactation (patients delivered, miscarried or breast-feed in three months before the treatment)
Patients are allergic to any ingredient of the medicine
Patients suffer from a disease requiring immediate blood transfusion
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
Alcohol or drug (such as aperient) abuse
Undiagnosed abnormal bleeding of the reproductive system.
Patients also participate in another clinical medicine study
Patients took part in another clinical trial that may influence this study before this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fengzh Feng, MD
Phone
18612671869
Ext
+86
Email
fengfzh@pumch.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Lan Zhu, MD
Email
zhu_julie@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lan Zhu, MD
Organizational Affiliation
Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences
City
Beijing
State/Province
China/Beiing
ZIP/Postal Code
100000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fengzh Feng, MD
Phone
18612671869
Ext
+86
Email
fengfzh@pumch.cn
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
26588841
Citation
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.
Results Reference
background
PubMed Identifier
23820898
Citation
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.
Results Reference
background
PubMed Identifier
26796059
Citation
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.
Results Reference
background
PubMed Identifier
24784716
Citation
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.
Results Reference
background
PubMed Identifier
27409646
Citation
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.
Results Reference
background
Links:
URL
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=26588841&query_hl=1
Description
Xenograft Model for Predicative Study of Uterine Fibroid Disease
URL
https://academic.oup.com/mend/article-lookup/doi/10.1210/me.2013-1059
Description
Uterine-Specific Loss of Tsc2 Leads to Myometrial Tumors in Both the Uterus and Lungs
URL
http://linkinghub.elsevier.com/retrieve/pii/S1521693415002308
Description
Medical Management for Uterine Leiomyomas
URL
https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2016-1395
Description
Lymphangioleiomyomatosis (LAM)
Learn more about this trial
Efficacy and Safety of Rapamycin (Sirolimus) in the Treatment of Symptomatic Uterine Fibroids and Leiomyomatosis
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