Clinical trial NCT05305001: Germline Mutations Associated With Hereditary Pancreatic Cancer in Unselected Patients With Pancreatic Cancer in Mexico
Official title: Prevalence Estimation of BRCA1, BRCA2 and Other Germline Mutations Associated With Hereditary Pancreatic Cancer Using a Comprehensive Gene Panel in an Unselected Cohort of Patients With Pancreatic Adenocarcinoma in Mexico
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pancreatic Cancer
Pancreatic Adenocarcinoma
Keywords: BRCA 1/2 germline mutations
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2022-03-31
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population will be patients who are diagnosed within 6 months of enrollment with pancreatic adenocarcinoma.

Brief summary: Pancreatic cancer is a highly lethal disease. The cause of pancreatic cancer is multifactorial. However, around 10% of cases are associated with hereditary predisposition. Germline mutations in BRCA1 and BRCA2, CDKN2A, STK11, DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2), PALB2, FANCC, FANCG, and ATM have been associated with an increased risk for pancreatic cancer. The prevalence of these germline mutations varies across populations. For instance, the prevalence of BRCA1/2 germline mutations in high-risk populations can be up to 20%. On the other hand, in unselected patient population, the prevalence of BRCA1/2 germline mutations is 5-7%. In Mexican population, data on the prevalence of BRCA1/2 germline mutations in patients with pancreatic cancer are lacking. Identification of BRCA germline mutations in patients with pancreatic cancer has implications for treatment. Also, it allows genetic testing and counselling for family members. This study will determine the prevalence of germline mutations associated with hereditary pancreatic cancer using a comprehensive gene panel in an unselected cohort of patients with pancreatic adenocarcinoma in Mexico.

Detailed description: This is an observational study to estimate the prevalence of germline mutations in patients with pancreatic cancer. Eighty four genes will be analyzed, all of which have been associated with hereditary cancer. The genes are included on Invitae Multi-Cancer Panel ®, performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology. The 84 genes include: AIP, ALK, APC, ATM, AXIN2, BAP1, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, CASR, CDC73, CDH1, CDK4, CDKN1B, CDKN1C, CDKN2A, CEBPA, CHEK2, CTNNA1, DICER1, DIS3L2, EGFR, EPCAM, FH, FLCN, GATA2, GPC3, GREM1, HOXB13, HRAS, KIT, MAX, MEN1, MET, MITF, MLH1, MSH2, MSH3, MSH6, MUTYH, NBN, NF1, NF2, NTHL1, PALB2, PDGFRA, PHOX2B, PMS2, POLD1, POLE, POT1, PRKAR1A, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RB1, RECQL4, RET, RUNX1, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, SMARCA4, SMARCB1, SMARCE1, STK11, SUFU, TERC, TERT, TMEM127, TP53, TSC1, TSC2, VHL, WRN, WT1.

Eligibility criteria: Inclusion Criteria:

* Female and male participants ≥ 18 years of age.
* Diagnosed within the previous 6 months with histologically confirmed pancreatic adenocarcinoma stage I to IV.
* Participant provides written informed consent for the study.
* Participant must agree to sample collection and genetic testing using the Invitae Multi-Cancer Panel ®.

Exclusion Criteria:

* Diagnosed with pancreatic adenocarcinoma more than 6 months before presenting to the clinical site.
* Diagnosed with intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, pancreatic neuroendocrine tumors.

Primary outcomes:
measure: BRCA 1/2 germline mutation prevalence
timeFrame: 15 months
Secondary outcomes:
measure: Other germline mutation prevalence
timeFrame: 15 months
measure: Clinical and pathological characteristics
timeFrame: 15 months
Other outcomes:
measure: The proportion of blood relatives of germline mutation carriers who accept genetic counseling and genetic testing
timeFrame: 15 months
measure: The proportion of germline mutation carriers who accept pancreatic cancer surveillance.
timeFrame: up to 15 months
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: Fidel D Huitzil Meléndez, MD
role: PRINCIPAL_INVESTIGATOR
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