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

NCT ID: NCT03781050

Last Updated: 2019-01-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-16
• Study Completion Date: 2022-07-01

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.

Conditions

Peutz-Jeghers Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rapamycin

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

Group Type: EXPERIMENTAL

Rapamycin

Intervention Type: DRUG

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

Interventions

Rapamycin

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

Other Intervention Names

Sirolimus

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Air Force General Hospital of the PLA

OTHER_GOV

Sponsor Role: collaborator

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jiaolin Zhou, MD

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences

Locations

Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences

Beijing, China/Beijing, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jiaolin Zhou, MD

Role: CONTACT

conniezhjl@yahoo.com

13910136704

Facility Contacts

Jiaolin Zhou, MD

Role: primary

conniezhjl@yahoo.com

13910136704

References

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.

Reference Type: BACKGROUND

PMID: 28653895 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15261145 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9425897 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19147279 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19434632 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HS-1607

Identifier Type: -

Identifier Source: org_study_id