Clinical Trial: Pilot Study of mTOR Inhibitor Therapy in Peutz-Jeghers Syndrome
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: Pilot Study of mTOR Inhibitor Therapy for Treatment of Intestinal Polyps in Peutz-Jeghers Syndrome
Brief Summary:
Pilot study, Open-label, Phase II study of Everolimus.
Objective:
To determine if Everolimus can diminish large gastrointestinal polyps in patients with Peutz-Jeghers Syndrome.
Methodology:
Polyp size and number will be compared to baseline by FDG-PET and CT and 12 months after treatment with Everolimus. Since this is a pilot study, the polyps prior to treatment will serve as the controls.
Detailed Summary:
Peutz-Jeghers Syndrome is a hereditary polyposis condition in which hamartomatous tumors develop in many tissues of the body. These tumors are benign but frequently cause gastrointestinal obstruction and bleeding beginning in the 2nd-3rd decades of life necessitating surgical intervention. Unfortunately, a recent study showed that the lifetime risk of cancers that arise in Peutz-Jeghers Syndrome is 85% by age 70 years and is 60% by age 60 years (Hearle et al., 2006).
A working definition of PJS has been suggested by Giardiello et al ,1987(www.genetests.com):
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For individuals with a histopathologically confirmed hamartoma, a definite diagnosis of PJS requires two of the following three findings:
- Family history consistent with autosomal dominant inheritance
- Mucocutaneous hyperpigmentation (although this can fade with age)
- Small-bowel polyposis
- For individuals without histopathologic verification of hamartomatous polyps, a probable diagnosis of PJS can be made based on the presence of two of the three clinical criteria above.
- For individuals without a family history of PJS, diagnosis depends upon the presence of two or more histologically verified Peutz-Jeghers-type hamartomatous polyps (Tomlinson & Houlston 1997).
- For individuals with a first-degree relative with PJS, presence of mucocutaneous hyperpigmentation is sufficient for presumptive diagnosis.
Recently, rapamycin (Rapamune, Wyeth), an FDA-approved drug for use in ort
Sponsor: University of Utah
Current Primary Outcome: The Size of Intestinal Polyps [ Time Frame: 24 months ]
Original Primary Outcome: To evaluate if RAD001 can decrease the size and/or number of intestinal polyps in patients with Peutz-Jeghers Syndrome. [ Time Frame: 2011 ]
Current Secondary Outcome:
Original Secondary Outcome:
- To evaluate if increased glucose uptake by hamartomas in Peutz-Jeghers syndrome patients due to mutations in STK11, which is involved in glucose homeostasis, renders them FDG avid [ Time Frame: 2011 ]
- To evaluate if RAD001 decreases mTOR signaling in intestinal polyps of Peutz-Jeghers syndrome patients. [ Time Frame: 2011 ]
- To evaluate if RAD001 increases apoptosis of intestinal polyps of Peutz-Jeghers syndrome patients. [ Time Frame: 2011 ]
- To evaluate FDG-PET as a tool for detecting intestinal polyps [ Time Frame: 2011 ]
Information By: University of Utah
Dates:
Date Received: November 17, 2008
Date Started: November 2008
Date Completion:
Last Updated: July 19, 2013
Last Verified: July 2013