Peutz-Jeghers SyndromePhase 4NCT03781050
Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome
A Phase 4 study testing Rapamycin in people with Peutz-Jeghers Syndrome, run by Peking Union Medical College Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Peutz-Jeghers Syndrome
- What is being tested?
- Rapamycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 16 Sep 2018to 1 Jul 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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),
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences
Beijing, China/Beijing, 100000
Jiaolin Zhou, MD, 13910136704, conniezhjl@yahoo.com
About this study
A prospective non-randomized open label single arm clinical trial to examine the efficacy and safety of sirolimus in patients with Peutz-Jeghers Syndrome.
Read the 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
- Being tested
- Rapamycin
- Keywords
- Peutz-Jeghers Syndrome (PJS), Rapamycin (sirolimus), Mammalian target of rapamycin (mTOR) inhibitor, Treatment
- Medical subject headings
- Peutz-Jeghers Syndrome, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RapamycinDrug
Also called Sirolimus
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The time from start of therapy to 1 year
Secondary outcomes (6)
Concentration of hemoglobin in blood
The value indicates the amount of gastrointestinal bleeding.
Measured: The time from start of therapy to 1 year
Concentration of albumin in blood
The value indicates the status of nutrition.
Measured: The time from start of therapy to 1 year
Concentration of hsCRP in blood
The value indicates the level of inflammation.
Measured: The time from start of therapy to 1 year
Visual analogue score (VAS)
The value indicates the level of pain.
Measured: The time from start of therapy to 1 year
Dermatology life quality index (DLQI)
The value indicates the status of hyperpigmented macules on the lips and oral mucosa.
Measured: The time from start of therapy to 1 year
Adverse events
To evaluate safety
Measured: The time from start of therapy to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start16 Sep 2018
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Peutz-Jeghers SyndromeStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Air Force General Hospital of the PLA, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Responsible party
- Sponsor
- Investigators
- Jiaolin Zhou, MD, Principal investigator, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03781050
- Sponsor's protocol ID
- HS-1607
- Status last verified
- Jan 2019
- First submitted
- 6 Dec 2018
- Last updated
- 23 Jan 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 28653895Shaw 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.
PubMed 15261145Jenne 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.
PubMed 9425897Wei 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.
PubMed 19147279Robinson 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.
PubMed 19434632
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome
- ClinicalTrials.gov ID
- NCT03781050
- Acronym / sponsor ID
- HS-1607
- Conditions
- Peutz-Jeghers Syndrome
- Keywords
- Peutz-Jeghers Syndrome (PJS), Rapamycin (sirolimus), Mammalian target of rapamycin (mTOR) inhibitor, Treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Collaborators
- Air Force General Hospital of the PLA, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Study start
- 16 Sep 2018 (actual)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Jul 2022 (estimated)
- First posted
- 19 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rapamycin | Experimental | Drug: RapamycinFor 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
Key exclusion criteria (14 listed)
- 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:
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 |
|---|---|---|
| RapamycinAlso: SirolimusFor 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 |
Primary outcome
Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps
Time frame: The time from start of therapy to 1 year
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.
6 secondary outcomes
Concentration of hemoglobin in blood
Time frame: The time from start of therapy to 1 year
Concentration of albumin in blood
Time frame: The time from start of therapy to 1 year
Concentration of hsCRP in blood
Time frame: The time from start of therapy to 1 year
Visual analogue score (VAS)
Time frame: The time from start of therapy to 1 year
Dermatology life quality index (DLQI)
Time frame: The time from start of therapy to 1 year
Adverse events
Time frame: The time from start of therapy to 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2019.
- Background: PubMed 28653895Chen 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.
- Background: PubMed 15261145Shaw 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.
- Background: PubMed 9425897Jenne 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.
- Background: PubMed 19147279Wei 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.
- Background: PubMed 19434632Robinson 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.
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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.
Jiaolin Zhou, MD principal investigator
Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rapamycin in people with Peutz-Jeghers Syndrome, run by Peking Union Medical College Hospital at 1 site in China.
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 11 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 23 Jan 2019. 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 China. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jiaolin Zhou, MD (13910136704, conniezhjl@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps (time frame: The time from start of therapy to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03781050, which also lists 5 linked publications.
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 23 Jan 2019.