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

NCT03781050 | Unknown Phase 4

• 1 other identifier: HS-1607
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Peutz-Jeghers Syndrome

Keywords

Peutz-Jeghers Syndrome (PJS); Rapamycin (sirolimus); Mammalian target of rapamycin (mTOR) inhibitor; Treatment

Outcome Measures

Primary Outcomes (1)

• 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.

  The time from start of therapy to 1 year

Secondary Outcomes (6)

• Concentration of hemoglobin in blood

  The time from start of therapy to 1 year

• Concentration of albumin in blood

  The time from start of therapy to 1 year

• Concentration of hsCRP in blood

  The time from start of therapy to 1 year

• Visual analogue score (VAS)

  The time from start of therapy to 1 year

• Dermatology life quality index (DLQI)

  The time from start of therapy to 1 year

Study Arms (1)

Rapamycin

EXPERIMENTAL

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

Drug: Rapamycin

Interventions

Rapamycin 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

Also known as: Sirolimus

Rapamycin

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Air Force General Hospital of the PLA: collaborator
• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: collaborator

Study Sites (1)

Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences

Beijing, China/Beijing, 100000, China

RECRUITING

Related Publications (5)

• 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.

  PMID: 28653895 BACKGROUND

• 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.

  PMID: 15261145 BACKGROUND

• 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.

  PMID: 9425897 BACKGROUND

• 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.

  PMID: 19147279 BACKGROUND

• 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.

  PMID: 19434632 BACKGROUND

MeSH Terms

Conditions

Peutz-Jeghers Syndrome; Hereditary Sensory and Autonomic Neuropathies

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Neoplastic Syndromes, Hereditary; Neoplasms; Intestinal Polyposis; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lentigo; Melanosis; Hyperpigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Jiaolin Zhou, MD

  Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiaolin Zhou, MD

CONTACT

13910136704; conniezhjl@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: December 19, 2018
• Study Start: September 16, 2018
• Primary Completion: January 1, 2022
• Study Completion: July 1, 2022
• Last Updated: January 23, 2019

Record last verified: 2019-01

Locations

CN (1)