Familial Adenomatous Poliposys Italian Network (Rete Italiana Poliposi Adenomatosa Familiare)

NCT07461246 | Active Not Recruiting

• 1 other identifier: INT 35/24
• Study Type: observational
• Target: 1,500
• Locations: 1 country
• Sites: 1

Brief Summary

RIPAF (Rete Italiana Poliposi Adenomatosa Familiare) is a national, multicenter observational registry designed to establish a coordinated Italian network for the management of Familial Adenomatous Polyposis (FAP) and related adenomatous polyposis syndromes. The registry includes patients with APC-related FAP (classic and attenuated forms), MUTYH-associated polyposis (MAP), and adenomatous polyposis not associated with APC or MUTYH mutations (NAMP), including cases linked to other susceptibility genes or without identified pathogenic variants. The study combines retrospective and prospective data collection across 28 Italian centers. Its primary purpose is to generate standardized, large-scale clinical data to better characterize disease presentation and evolution, evaluate current surveillance and surgical strategies, and assess oncological outcomes and quality-of-care indicators in real-world practice. The registry will collect detailed information on genotype-phenotype correlations, colorectal and upper gastrointestinal cancer incidence, desmoid tumor development, timing and type of prophylactic surgery, postoperative outcomes, and long-term survival. Additional objectives include evaluating adherence to surveillance guidelines, timing of genetic diagnosis, and preventive surgical uptake among at-risk relatives. By harmonizing data collection and promoting collaboration among referral centers, RIPAF aims to reduce variability in clinical management across Italy, improve risk stratification and decision-making, and create a national platform to support future multicenter research initiatives and international collaborations in hereditary colorectal cancer syndromes.

Conditions

MUTYH-Associated Polyposis (MAP); Familial Adenomatous Polyposis (FAP); Attenuated Familial Adenomatous Polyposis (AFAP); Non-APC/MUTYH Associated Polyposis (NAMP); Gardner Syndrome; Turcot Syndrome; Colorectal Cancer; Desmoid Tumor; Desmoid-Type Fibromatosis; Duodenal Adenoma; Upper Gastrointestinal Polyposis; Hereditary Colorectal Cancer Syndrome; Hereditary Polyposis Syndrome

Keywords

Familial Adenomatous Polyposis; APC gene; MUTYH gene; POLE gene; POLD1 gene; NTHL1 gene; MSH3 gene; GREM1 gene; Polyposis Registry; National Registry; Multicenter Registry; Colorectal Cancer Prevention; Prophylactic Colectomy; Ileorectal Anastomosis; Ileal Pouch-Anal Anastomosis; Desmoid Fibromatosis; Genotype-Phenotype correlation; Hereditary Cancer Syndrome; Cancer Surveillance Strategy; Quality of Care Indicators; Natural History Study; REDCap Database; European Reference Network; ERN GENTURIS

Outcome Measures

Primary Outcomes (2)

• Natural History Characterization

  This includes comprehensive analysis of genotype-phenotype correlations, age at diagnosis, polyp burden at diagnosis and over time, colorectal cancer incidence, and prevalence and timing of extracolonic manifestations across all polyposis subtypes.

  Throughout study period, up to 36 months and extended follow-up

• Quality of Care Indicators

  This encompasses measurement of time intervals from symptom onset to genetic diagnosis, adherence to surveillance colonoscopy and upper endoscopy protocols, time from diagnosis to prophylactic surgery in appropriate candidates, and rate of prophylactic surgery uptake in at-risk family members.

  Throughout study period, up to 36 months

Secondary Outcomes (8)

• Overall Survival

  Up to 36 months and extended long-term follow-up

• Cancer-Specific Survival

  Up to 36 months and extended long-term follow-up

• Desmoid Tumor Outcomes

  Up to 36 months and extended long-term follow-up

• Surgical Outcomes

  Up to 36 months and extended long-term follow-up

• Surgical approach Outcomes

  Up to 36 months and extended long-term follow-up

Eligibility Criteria

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

Study Population

Patients will be categorized into cohorts based on genetic and phenotypic characteristics. The FAP Classic Phenotype cohort includes patients with pathogenic APC variants presenting with more than 100 colorectal adenomas and classic extracolonic manifestations. The AFAP Attenuated Phenotype cohort comprises patients with pathogenic APC variants presenting with 10-99 colorectal adenomas and later age of onset. The MAP cohort consists of patients with biallelic MUTYH pathogenic variants presenting with 10 to a few hundred polyps of adenomatous, hyperplastic, or serrated histology. The NAMP cohort includes patients without identified APC or MUTYH variants, which may include variants in POLE, POLD1, NTHL1, MSH3, GREM1, or cases with no identified genetic defect. Additional clinical variants include Gardner Syndrome (FAP with desmoid tumors, fibromas, cysts, osteomas) and Turcot Syndrome (FAP with CNS neoplasms, particularly medulloblastoma).

You may qualify if:

• patients with documented colorectal polyposis (\>10 synchronous adenomas or ≥20 adenomas across multiple colonoscopies);
• patients who have undergone genetic testing with the following results: a pathogenic variant (PV) in APC (FAP); biallelic pathogenic variants in MUTYH (MAP); other pathogenic variants identified in genes such as POLE, POLD1, NTHL1, MSH3, and GREM1;
• patients in whom no pathogenic variants have been identified in known genes (NAMP);
• histologically, the majority of polyps must be adenomas.

You may not qualify if:

• Patients whose polyp burden does not meet the specified thresholds or whose polyps are predominantly non-adenomatous (hyperplastic, serrated, hamartomatous).
• Patients who refuse to provide informed consent.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• IRCCS Ospedale San Raffaele: collaborator
• Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale: collaborator

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

MeSH Terms

Conditions

Adenomatous Polyposis Coli; Attenuated familial adenomatous polyposis; Gardner Syndrome; Turcot syndrome; Colorectal Neoplasms; Desmoid Tumors; Polyposis Syndrome, Hereditary Mixed, 1; Neoplastic Syndromes, Hereditary

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Abnormalities, Multiple; Congenital Abnormalities; Rectal Diseases; Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue

Study Officials

• Marco Vitellaro, MD

  IRCCS Istituto Nazionale dei Tumori

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: OTHER
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 10, 2026
• Study Start: May 13, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 10, 2026

Record last verified: 2026-02

Locations

IT (1)