Clinical trial NCT03781050: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Peutz-Jeghers Syndrome
Keywords: Peutz-Jeghers Syndrome (PJS)
Rapamycin (sirolimus)
Mammalian target of rapamycin (mTOR) inhibitor
Treatment
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Air Force General Hospital of the PLA
name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
First posted: 2018-12-19
Enrollment: 10
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps
timeFrame: The time from start of therapy to 1 year
Secondary outcomes:
measure: Concentration of hemoglobin in blood
timeFrame: The time from start of therapy to 1 year
measure: Concentration of albumin in blood
timeFrame: The time from start of therapy to 1 year
measure: Concentration of hsCRP in blood
timeFrame: The time from start of therapy to 1 year
measure: Visual analogue score (VAS)
timeFrame: The time from start of therapy to 1 year
measure: Dermatology life quality index (DLQI)
timeFrame: The time from start of therapy to 1 year
measure: Adverse events
timeFrame: The time from start of therapy to 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences
state: China/Beijing
Study officials:
affiliation: Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences
name: Jiaolin Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.