| Registry | NCT07889596 |
|---|---|
| Status | Not yet recruiting |
| Study type | Observational |
| Enrollment | 1000 (Estimated) |
| Sponsor | First People's Hospital of Hangzhou (Other) |
| Conditions | Peutz-Jeghers Syndrome |
| Dates | start 2026-10-01 (estimated), primary completion 2046-10-01 (estimated), completion 2056-10-01 (estimated), first posted 2026-10-22, last updated 2026-10-22 |
| Locations | 9 sites in China |
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All trials for Peutz-Jeghers Syndrome
This prospective, observational patient registry will enroll approximately 1,000 individuals with a clinical or molecular diagnosis of Peutz-Jeghers syndrome (PJS) at participating hospitals in China. The registry will collect standardized clinical information, existing genetic test reports, family history, and longitudinal outcomes. The primary objective is to estimate the 10-year cumulative incidence of a first invasive malignancy after enrollment among participants without a previous malignancy or an unresolved suspected malignancy at baseline, accounting for death as a competing event. Secondary objectives address organ-specific malignancies, new primary cancers in participants with a cancer history, mortality, major polyp-related complications, and clinical and STK11 variant characteristics. Participants may be followed for up to 20 years. Biospecimen donation, additional baseline sampling, research sequencing, and patient-derived organoid studies are optional and require the corresponding consent. Refusal of an optional component does not preclude participation in the clinical registry. No treatment or clinical surveillance strategy is assigned by the study.
Peutz-Jeghers syndrome is a rare inherited tumor-predisposition syndrome associated with gastrointestinal hamartomatous polyps, mucocutaneous pigmentation, and increased risks of several malignancies. This multicenter registry will document the clinical course of enrolled patients receiving usual care and will support carefully defined genotype-phenotype and translational research. It is a hospital-based, non-probability sample and is not designed to provide a probability-representative estimate for the entire Chinese PJS population.
The purpose of this study is to establish a nationwide multicenter registry of patients with PJS, integrating standardized clinical information, existing genetic reports, optional biospecimen studies and prospective follow-up. The primary objective is to estimate 10-year cumulative incidence of a first invasive malignancy among participants without previous or unresolved suspected malignancy at baseline. The study will support defined genotype-phenotype and translational analyses; it does not assign treatment or clinical surveillance.
Specific study objectives are listed below:
1. Establish a standardized PJS clinical database to define the clinical characteristics and natural history of the disease in Chinese patients.
2. Analyze the landscape of STK11 gene variants and the relationship between genotype and clinical phenotype.
3. Establish an optional biobank of patients with PJS, using separately consented specimens, to provide resources for approved research.
4. Establish separately consented patient-derived organoid models to investigate disease mechanisms and in vitro drug responses without directing patient treatment.
5. Explore the development of a precision management system. The workflow includes consecutive recruitment, diagnostic confirmation, core registry consent, baseline clinical-data abstraction, prospective follow-up and outcome review. Biospecimen collection, research sequencing and organoid studies are optional components; refusal does not preclude enrollment.
The planned enrollment period is October 2026 through September 2036, with approximately 100 new participants per year across all sites combined. Each site may begin recruitment only after the applicable ethics and institutional permissions are in place. The baseline date is the date of valid consent, eligibility confirmation, and registry enrollment. Historical medical information will be abstracted at baseline and distinguished from prospectively observed events. Participants will be contacted approximately every 12 months through routine visits, telephone, or institution-approved remote methods. Additional clinically indicated visits will be recorded without imposing a research surveillance schedule.
All eligible, consenting participants contribute to the clinical registry. Participants with previous malignancy remain eligible but do not contribute to the primary first-malignancy risk set. Unaffected or diagnostically unconfirmed relatives will not be independently enrolled under this version of the protocol. A relative who independently meets the clinical or molecular diagnostic criteria may enroll with separate consent and an individual identifier linked to the appropriate pedigree identifier. Genetic variants of uncertain significance alone do not establish molecular eligibility.
The primary outcome is a first invasive malignancy diagnosed after enrollment among participants with no previous malignancy and no unresolved suspected malignancy at baseline. Death before malignancy is treated as a competing event. New primary malignancies will be distinguished from benign lesions, in situ disease, recurrence, progression, and metastasis. Outcome evidence and dates will be reviewed by appropriate clinicians. The primary analysis will estimate the cumulative incidence function at 10 years using an Aalen-Johansen approach, with uncertainty accounting for family clustering when supported by the data. Attained-age analyses will use delayed entry at enrollment and will not treat the period before enrollment as prospectively observed person-time.
Clinical and genetic associations will account for family relationships, recruitment pathway, center, and relevant prespecified covariates. STK11 germline variants will be classified using the ACMG/AMP framework and applicable subsequent guidance, with the reference sequence, testing scope, evidence, and interpretation date documented. Germline and tumor-only findings will be distinguished. Untested participants, participants with limited testing, those with variants of uncertain significance, and those with adequately evaluated negative findings will not be combined into a single wild-type group. Exploratory analyses will be limited by the available events and independent families, and multiplicity and model optimism will be addressed.
Optional biospecimen studies prioritize clinical residual material. No research-only tissue biopsy or enlargement of a clinical resection is permitted. Additional research sampling under this protocol is limited to a single baseline collection: in suitable consenting adults, up to 10 mL of peripheral blood in total or 2mL of saliva, approximately 30 mL of urine, approximately 5 g of stool, and, where clinically appropriate, one cervical or vaginal swab at one documented site during an already indicated clinical examination. No additional examination is required solely to obtain a genital swab. No additional research blood draw or genital swab will be performed in minors under this protocol. Minors may provide clinically residual specimens and optional noninvasive urine or stool samples, with appropriate parental/guardian consent and age-appropriate assent. Repeat additional research sampling requires a protocol and consent amendment. Genomic sequencing and organoid work require their specific optional consent.
Research sequencing, multi-omics, and patient-derived organoid or tumor-organoid studies will be performed only in authorized, suitable subsets. Laboratory and analytical methods will distinguish biological participants from repeated specimens or culture wells. Predictive biomarker analyses require pre-outcome specimens and family-separated validation. Research findings will not direct clinical treatment; clinically meaningful findings considered for return require appropriate confirmation, counseling, and the participant's documented preference. The registry does not plan public or external sharing of individual participant data. Any use beyond the approved purpose and authorized project collaboration will require a separate institutional, regulatory, and consent assessment.
The planned primary completion date is October 2046, allowing approximately 10 years of primary outcome observation after the final planned enrollment in 2036. The planned study completion date is October 2056, allowing up to 20 years of follow-up per participant. Earlier stage-specific reports will describe the actual available observation time and will not be labeled complete 10-year follow-up for all participants.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Peutz-Jeghers syndrome | Individuals meeting protocol-defined clinical diagnostic criteria or carrying a confirmed germline pathogenic or likely pathogenic STK11 variant associated with PJS. Participants with and without previous cancer may enroll. Optional biospecimen and genetic components do not determine clinical registry eligibility. |
Sex: All
Inclusion Criteria: * A clinical diagnosis of PJS meeting at least one of the following: two or more histologically confirmed Peutz-Jeghers polyps; any number of Peutz-Jeghers polyps and a family history of PJS; characteristic mucocutaneous pigmentation and a family history of PJS; or any number of Peutz-Jeghers polyps together with characteristic mucocutaneous pigmentation. Alternatively, a molecular diagnosis established by a confirmed germline pathogenic or likely pathogenic STK11 variant associated with PJS, interpreted by appropriately qualified professionals. * Valid written informed consent for the core clinical registry from the participant or the legally appropriate guardian, with age- and capacity-appropriate information and assent when applicable. * Minimum clinical or genetic documentation sufficient to confirm eligibility and agreement to at least one feasible method of longitudinal contact or record-based follow-up within the approved consent. Biospecimen donation, availability of all specimen types, and participation in research sequencing or organoid experiments are not required for clinical registry enrollment. Exclusion Criteria: * Neither the clinical nor molecular diagnostic pathway can be confirmed. A variant of uncertain significance alone does not satisfy molecular eligibility. * Absence of valid consent for the core registry. Duplicate records of the same individual will be merged rather than counted as additional participants. Inability or refusal to undergo an optional sample procedure is not a registry exclusion criterion. Procedure-specific safety restrictions affect that procedure only.
| Facility | City | Country | Status |
|---|---|---|---|
| Fujian Maternity and Child Health Care Hospital | Fuzhou, Fujian | China | |
| Sun Yat-sen University Cancer Center | Guangzhou, Guangdong | China | |
| Qilu Hospital of Shandong University | Jinan, Shandong | China | |
| First People's Hospital of Hangzhou | Hangzhou, Zhejiang | China | |
| Zhejiang Cancer Hospital | Hangzhou, Zhejiang | China | |
| Peking University Third Hospital | Beijing | China | |
| Fudan University Shanghai Cancer Center | Shanghai | China | |
| Obstetrics & Gynecology Hospital of Fudan University | Shanghai | China | |
| The Second Hospital of Tianjin Medical University | Tianjin | China |