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Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome

Primary Purpose

Peutz-Jeghers Syndrome

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Rapamycin
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peutz-Jeghers Syndrome focused on measuring Peutz-Jeghers Syndrome (PJS), Rapamycin (sirolimus), Mammalian target of rapamycin (mTOR) inhibitor, Treatment

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients are diagnosed with PJS.
  • Patients have gastrointestinal polyps related syndromes, including abdominal pain, abdominal distension, gastrointestinal bleeding, etc, with imageological examination suggesting intestinal obstruction or intussusception; or whose symptoms recur after previous digestive endoscopic treatment and surgery; or who are inappropriate or unwilling to accept the above treatment again and wish to receive pharmacotherapy.
  • Conventional treatment didn't work well in patients combined with PJS-related tumors.
  • Physical condition (ECGO): 0~3

  • Organ function is good and biochemical indices meet the following conditions:

    • AST≤2.5×upper limit of normal value (ULN),
    • ALT≤2.5×upper limit of normal value (ULN),
    • Serum total bilirubin (TSB)≤1.5×upper limit of normal value (ULN),
    • Creatinine≤1.5×upper limit of normal value (ULN).
  • No other medications have been received for intestinal polyps within 3 months prior to the clinical trial.
  • Patients participate in the trial voluntarily and have signed the informed consent by the participant or his/her legal guardian.

Exclusion Criteria:

  • Patients underwent a surgery within 2 weeks.
  • Patients may need emergency surgery in the near future.
  • Patients are allergic to any ingredient of rapamycin.
  • Patients suffer from a disease requiring immediate blood transfusion.

  • Patients suffer from any disease or condition that may impact implementation of the study or interpretation of the results. This type of diseases includes:

    • Known severe blood coagulation disorders
    • Known anemia that is not caused by intestinal polyps
    • Known hemoglobinopathy
    • Other gastrointestinal infectious diseases
    • Serious heart, liver, kidney and other concomitant diseases that may endanger lives
  • Patients are in pregnancy and lactation.
  • Alcohol or drug (such as aperient) abuse
  • Patients took part in another clinical trial that may influence this study.
  • The researchers believe that there are other unfavorable reasons for the patient to become a subject.

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

For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months For adults: rapamycin, 2 mg a day, orally, for at least 6 months

Outcomes

Primary Outcome Measures

Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps
Lesion load (cm2) = A+B. A = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by abdomen and pelvis MRI or small bowel CT reconstruction (in cm2). B = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by digestive endoscope (in cm2). Remarks: 1. If it is impossible to evaluate 3 or more lesions, results of the actual number of lesions should be taken as valid; 2. Lesions evaluated should be correspondent before and after treatment. If the lesion is difficult to assess after treatment, it should be ruled out from the assessment.

Secondary Outcome Measures

Concentration of hemoglobin in blood
The value indicates the amount of gastrointestinal bleeding.
Concentration of albumin in blood
The value indicates the status of nutrition.
Concentration of hsCRP in blood
The value indicates the level of inflammation.
Visual analogue score (VAS)
The value indicates the level of pain.
Dermatology life quality index (DLQI)
The value indicates the status of hyperpigmented macules on the lips and oral mucosa.
Adverse events
To evaluate safety

Full Information

First Posted
December 6, 2018
Last Updated
January 18, 2019
Sponsor
Peking Union Medical College Hospital
Collaborators
Air Force General Hospital of the PLA, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT03781050
Brief Title
Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome
Official Title
Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 16, 2018 (Actual)
Primary Completion Date
January 1, 2022 (Anticipated)
Study Completion Date
July 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital
Collaborators
Air Force General Hospital of the PLA, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

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 single arm clinical trial to examine the efficacy and safety of sirolimus in patients with Peutz-Jeghers Syndrome.
Detailed Description
PJS (Peutz-Jeghers Syndrome) is mostly caused by mutations in Lkb1 gene, which leads to an increased activity of mTOR pathway, thus making mTOR inhibitor (sirolimus) a promising candidate in treatment and prevention of PJS. The efficacy of sirolimus (rapamycin) on PJS has been demonstrated in mouse model, but no clinical trials have been reported. Our study was designed as a prospective non-randomized open label single arm clinical trial to examine its efficacy and safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peutz-Jeghers Syndrome
Keywords
Peutz-Jeghers Syndrome (PJS), Rapamycin (sirolimus), Mammalian target of rapamycin (mTOR) inhibitor, Treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rapamycin
Arm Type
Experimental
Arm Description
For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months For adults: rapamycin, 2 mg a day, orally, for at least 6 months
Intervention Type
Drug
Intervention Name(s)
Rapamycin
Other Intervention Name(s)
Sirolimus
Intervention Description
For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months For adults: rapamycin, 2 mg a day, orally, for at least 6 months
Primary Outcome Measure Information:
Title
Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps
Description
Lesion load (cm2) = A+B. A = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by abdomen and pelvis MRI or small bowel CT reconstruction (in cm2). B = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by digestive endoscope (in cm2). Remarks: 1. If it is impossible to evaluate 3 or more lesions, results of the actual number of lesions should be taken as valid; 2. Lesions evaluated should be correspondent before and after treatment. If the lesion is difficult to assess after treatment, it should be ruled out from the assessment.
Time Frame
The time from start of therapy to 1 year
Secondary Outcome Measure Information:
Title
Concentration of hemoglobin in blood
Description
The value indicates the amount of gastrointestinal bleeding.
Time Frame
The time from start of therapy to 1 year
Title
Concentration of albumin in blood
Description
The value indicates the status of nutrition.
Time Frame
The time from start of therapy to 1 year
Title
Concentration of hsCRP in blood
Description
The value indicates the level of inflammation.
Time Frame
The time from start of therapy to 1 year
Title
Visual analogue score (VAS)
Description
The value indicates the level of pain.
Time Frame
The time from start of therapy to 1 year
Title
Dermatology life quality index (DLQI)
Description
The value indicates the status of hyperpigmented macules on the lips and oral mucosa.
Time Frame
The time from start of therapy to 1 year
Title
Adverse events
Description
To evaluate safety
Time Frame
The time from start of therapy to 1 year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients are diagnosed with PJS. Patients have gastrointestinal polyps related syndromes, including abdominal pain, abdominal distension, gastrointestinal bleeding, etc, with imageological examination suggesting intestinal obstruction or intussusception; or whose symptoms recur after previous digestive endoscopic treatment and surgery; or who are inappropriate or unwilling to accept the above treatment again and wish to receive pharmacotherapy. Conventional treatment didn't work well in patients combined with PJS-related tumors. Physical condition (ECGO): 0~3 Organ function is good and biochemical indices meet the following conditions: AST≤2.5×upper limit of normal value (ULN), ALT≤2.5×upper limit of normal value (ULN), Serum total bilirubin (TSB)≤1.5×upper limit of normal value (ULN), Creatinine≤1.5×upper limit of normal value (ULN). No other medications have been received for intestinal polyps within 3 months prior to the clinical trial. Patients participate in the trial voluntarily and have signed the informed consent by the participant or his/her legal guardian. Exclusion Criteria: Patients underwent a surgery within 2 weeks. Patients may need emergency surgery in the near future. Patients are allergic to any ingredient of rapamycin. Patients suffer from a disease requiring immediate blood transfusion. Patients suffer from any disease or condition that may impact implementation of the study or interpretation of the results. This type of diseases includes: Known severe blood coagulation disorders Known anemia that is not caused by intestinal polyps Known hemoglobinopathy Other gastrointestinal infectious diseases Serious heart, liver, kidney and other concomitant diseases that may endanger lives Patients are in pregnancy and lactation. Alcohol or drug (such as aperient) abuse Patients took part in another clinical trial that may influence this study. The researchers believe that there are other unfavorable reasons for the patient to become a subject.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jiaolin Zhou, MD
Phone
13910136704
Email
conniezhjl@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jiaolin Zhou, 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/Beijing
ZIP/Postal Code
100000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiaolin Zhou, MD
Phone
13910136704
Email
conniezhjl@yahoo.com

12. IPD Sharing Statement

Citations:
PubMed Identifier
28653895
Citation
Chen HY, Jin XW, Li BR, Zhu M, Li J, Mao GP, Zhang YF, Ning SB. Cancer risk in patients with Peutz-Jeghers syndrome: A retrospective cohort study of 336 cases. Tumour Biol. 2017 Jun;39(6):1010428317705131. doi: 10.1177/1010428317705131.
Results Reference
background
PubMed Identifier
15261145
Citation
Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA, Cantley LC. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell. 2004 Jul;6(1):91-9. doi: 10.1016/j.ccr.2004.06.007.
Results Reference
background
PubMed Identifier
9425897
Citation
Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, Muller O, Back W, Zimmer M. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998 Jan;18(1):38-43. doi: 10.1038/ng0198-38.
Results Reference
background
PubMed Identifier
19147279
Citation
Wei C, Amos CI, Zhang N, Zhu J, Wang X, Frazier ML. Chemopreventive efficacy of rapamycin on Peutz-Jeghers syndrome in a mouse model. Cancer Lett. 2009 May 18;277(2):149-54. doi: 10.1016/j.canlet.2008.11.036. Epub 2009 Jan 14.
Results Reference
background
PubMed Identifier
19434632
Citation
Robinson J, Lai C, Martin A, Nye E, Tomlinson I, Silver A. Oral rapamycin reduces tumour burden and vascularization in Lkb1(+/-) mice. J Pathol. 2009 Sep;219(1):35-40. doi: 10.1002/path.2562.
Results Reference
background

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Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome

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