Peutz-Jeghers SyndromePhase 2NCT00811590
Pilot Study of mTOR Inhibitor Therapy in Peutz-Jeghers Syndrome
A Phase 2 study testing Everolimus in people with Peutz-Jeghers Syndrome, run by University of Utah at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peutz-Jeghers Syndrome
- What is being tested?
- Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Mar 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Yes/No (Response of "no" = patient ineligible)
- Patients who are 18 years or older with a clinical or genetic diagnosis of Peutz-Jeghers Syndrome.
- Patient has one or more intestinal polyps ≥ 5mm in maximum diameter by contrast enhanced CT scan that is not clinically indicated for removal or is beyond the reach of a push endoscope.
- Minimum of two weeks since any major surgery.
- Patient has had colonoscopy within the past 24 months and did not have high-grade dysplasia or colorectal cancers.
- WHO performance status £ 2
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- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hgb > 9 g/dL
- Adequate liver function as shown by: serum bilirubin ≤ 1.5 x upper limit of normal (ULN), and serum transaminases activity ≤ 2.5 x ULN.
- Patients must be able to provide written informed consent.
Who cannot join
- Yes/No (Response of "yes" = patient ineligible)
- Prior treatment with any investigational drug within the preceding 4 weeks
- Chronic treatment with systemic steroids or another immunosuppressive agent
- Patients should not receive immunization with attenuated live vaccines during study period or within one week of study entry
- Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
- Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
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- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia
- Severely impaired lung function
- Uncontrolled diabetes as defined by fasting serum glucose >1.5x ULN
- Any active (acute or chronic) or uncontrolled infection/ disorders.
- Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
- Liver disease such as cirrhosis, or severe hepatic impairment (Child-Pugh class C)
- A known history of HIV seropositivity
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis or on oral anti-vitamin K medication
- Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control throughout the trial and for 8 weeks after the last dose of study drug. (Women of childbearing potential must have a negative pregnancy test). Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
- Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception during the study and for 9 weeks after the end of treatment.
- Patients who have received treatment with an mTor inhibitor in the past 6 months.
- Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
- Patients who can not undergo FDG-PET are eligible to participate in this study for the purpose of the primary endpoint. Patient with the following will be excluded from FDG-PET piece of the study.
- Patients cannot have a serum glucose level greater than 200 mg/dl for FDG-PET imaging
- Patients who are too claustrophobic to undergo FDG-PET imaging
- Patients who will require conscious sedation to undergo FDG-PET imaging.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: Pilot Study of mTOR Inhibitor Therapy for Treatment of Intestinal Polyps in Peutz-Jeghers Syndrome
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.
Read the detailed description
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):
- 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 orthotopic transplant recipients, was successfully used in an off-label study of 5 individuals with a related condition called tuberous sclerosis in which the patients had subependymal giant cell astrocytomas that caused significant and insidious neurological problems such as hydrocephalus and seizures (Franz, et al. 2006). All astrocytoma lesions exhibited regression with treatment of oral rapamycin and in one case, necrosis. Treatment was well tolerated and may offer an alternative to operative therapy in tuberous sclerosis. Tuberous sclerosis is caused by germline mutations in the tuberous sclerosis 1 or 2 genes. These genes encode proteins that function downstream of STK11, the gene that is mutated in Peutz-Jeghers Syndrome. Mutations of STK11 or TSC1/2 leads to activation of mTOR (mammalian target of rapamycin). Dysregulation of mTOR has been demonstrated in several types of cancers and clinical trials are underway to see if inhibition of mTOR will be of benefit to a variety of cancer patients. A recent trial showed efficacy of everolimus in advanced renal cancer (Hudes, et al. 2007).
All of these studies will be performed on an outpatient basis.
- Conditions
- Peutz-Jeghers Syndrome
- Being tested
- Everolimus
- Keywords
- Cancer, Polyps
- Medical subject headings
- Peutz-Jeghers Syndrome, Neoplasms, Polyps
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called everolimus, Certican, Afinitor
Everolimus is a novel derivative of rapamycin. Everolimus has been in clinical development since 1996 as an immunosuppressant in solid organ transplantation. Since 2003, RAD001 is approved in Europe (trade name: Certican) via the Mutual Recognition Procedure (MRP) for the prevention of organ rejection in patients with renal and cardiac transplantation. Certican is also approved in Australia, South Africa, the Middle East, Central and South America, the Caribbean and some Asian countries.
Everolimus is being investigated as an anticancer agent based on its potential to act
- directly on the tumor cells by inhibiting tumor cell growth and proliferation
- indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell VEGF production and VEGF-induced proliferation of endothelial cells.
| Study group | Role | What they receive |
|---|---|---|
| All patients | Experimental | All participants enrolled. Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Size of Intestinal Polyps
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2008 (estimated)
- Study startNov 2008
- Primary completionMar 2011
- Study completionMar 2011
Why it stopped: The study was ended early due to low enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Peutz-Jeghers SyndromeStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Randall W Burt, MD, Principal investigator, Huntsman Cancer InstituteScott Kuwada, MD, Study chair, University of Hawaii
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00811590
- Sponsor's protocol ID
- HCI26943
- Status last verified
- Aug 2024
- First submitted
- 17 Nov 2008
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of mTOR Inhibitor Therapy for Treatment of Intestinal Polyps in Peutz-Jeghers Syndrome
- ClinicalTrials.gov ID
- NCT00811590
- Acronym / sponsor ID
- HCI26943
- Conditions
- Peutz-Jeghers Syndrome
- Keywords
- Cancer, Polyps
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was ended early due to low enrollment.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Nov 2008
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 19 Dec 2008 (estimated)
- Results
- Posted 4 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
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):
- 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 orthotopic transplant recipients, was successfully used in an off-label study of 5 individuals with a related condition called tuberous sclerosis in which the patients had subependymal giant cell astrocytomas that caused significant and insidious neurological problems such as hydrocephalus and seizures (Franz, et al. 2006). All astrocytoma lesions exhibited regression with treatment of oral rapamycin and in one case, necrosis. Treatment was well tolerated and may offer an alternative to operative therapy in tuberous sclerosis. Tuberous sclerosis is caused by germline mutations in the tuberous sclerosis 1 or 2 genes. These genes encode proteins that function downstream of STK11, the gene that is mutated in Peutz-Jeghers Syndrome. Mutations of STK11 or TSC1/2 leads to activation of mTOR (mammalian target of rapamycin). Dysregulation of mTOR has been demonstrated in several types of cancers and clinical trials are underway to see if inhibition of mTOR will be of benefit to a variety of cancer patients. A recent trial showed efficacy of everolimus in advanced renal cancer (Hudes, et al. 2007).
All of these studies will be performed on an outpatient basis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All patients | Experimental | Drug: EverolimusAll participants enrolled. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Yes/No (Response of "no" = patient ineligible)
- Patients who are 18 years or older with a clinical or genetic diagnosis of Peutz-Jeghers Syndrome.
- Patient has one or more intestinal polyps ≥ 5mm in maximum diameter by contrast enhanced CT scan that is not clinically indicated for removal or is beyond the reach of a push endoscope.
- Minimum of two weeks since any major surgery.
- Patient has had colonoscopy within the past 24 months and did not have high-grade dysplasia or colorectal cancers.
Key exclusion criteria (24 listed)
- Yes/No (Response of "yes" = patient ineligible)
- Prior treatment with any investigational drug within the preceding 4 weeks
- Chronic treatment with systemic steroids or another immunosuppressive agent
- Patients should not receive immunization with attenuated live vaccines during study period or within one week of study entry
- Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: everolimus, Certican, AfinitorEverolimus is a novel derivative of rapamycin. Everolimus has been in clinical development since 1996 as an immunosuppressant in solid organ transplantation. Since 2003, RAD001 is approved in Europe (trade name: Certican) via the Mutual Recognition Procedure (MRP) for the prevention of organ rejection in patients with renal and cardiac transplantation. Certican is also approved in Australia, South Africa, the Middle East, Central and South America, the Caribbean and some Asian countries. Everolimus is being investigated as an anticancer agent based on its potential to act * directly on the tumor cells by inhibiting tumor cell growth and proliferation * indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell VEGF production and VEGF-induced proliferation of endothelial cells. | Drug | All patients |
Primary outcome
The Size of Intestinal Polyps
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Peutz-Jeghers Syndrome
Not yet recruitingObservational study
Chinese Multicenter Registry for Peutz-Jeghers Syndrome
Peutz-Jeghers Syndrome
RecruitingPhase 3
The Cancer of the Pancreas Screening-5 CAPS5)Study
Pancreas Cancer, Peutz-Jeghers Syndrome (PJS)
Active, not recruitingObservational study
The Pancreas Interception Center (PIC) for Early Detection, Prevention, and Novel Therapeutics
Pancreatic Ductal Adenocarcinoma, Pancreatic Cyst
RecruitingObservational study
Familial Investigations of Childhood Cancer Predisposition
Acute Leukemia, Adenomatous Polyposis
RecruitingObservational study
Pancreas Registry and High Risk Registry
Pancreas Cancer, Pancreatitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Randall W Burt, MD principal investigator
Huntsman Cancer Institute
Scott Kuwada, MD study chair
University of Hawaii
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus in people with Peutz-Jeghers Syndrome, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Size of Intestinal Polyps (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.