Pancreatic CancerNCT01103128
Validation of a Mouse Model of Pancreatic Carcinogenesis
An observational study of Pancreatic Cancer, run by Columbia University at 1 site in United States.
Trial summary
The primary aim of this study is to determine if mutations of BRCA1 and BRCA2 result in different precancerous pathways to pancreatic ductal adenocarcinoma (PDAC), as suggested in our validated mouse model. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pancreatic Cancer
- How many people
- 450 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to May 2013
- Phase
- Observational
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All subjects have a tissue-confirmed diagnosis of pancreatic adenocarcinoma, MCN or IPMN and underwent surgical resection for pancreatic adenocarcinoma, MCN or IPMN at Columbia-Presbyterian Medical Center.
Who may be able to join
- Tissue-confirmed diagnosis of pancreatic adenocarcinoma, MCN, or IPMN.
- Underwent surgical resection for pancreatic adenocarcinoma, MCN, or IPMN.
Who cannot join
- Unwilling to provide informed consent.
- Under the age of 18.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: BRCA1 and BRCA2 Genetic Mutations in Mucinous Versus Nonmucinous Precursor Lesions of the Pancreas: Validation of a Mouse Model of Pancreatic Carcinogenesis
The primary aim of this study is to determine if mutations of BRCA1 and BRCA2 result in different precancerous pathways to pancreatic ductal adenocarcinoma (PDAC), as suggested in our validated mouse model. Genomic DNA will be isolated on normal tissue obtained from patients who underwent pancreatic resection for PDAC, intraductal papillary mucinous neoplasm (IPMN) or mucinous cystic neoplasm (MCN). Tissue will be examined for the three most common founder mutations in Ashkenazi Jews. In the cases in which BRCA1 or BRCA2 mutations are found, heterozygote normal and abnormal tissue will be examined to look for mutations in the other BRCA1 or BRCA2 allele. The interaction between other cancer causing genes with BRCA1/2 will also be evaluated by comparing the sequences of the other genes in pre-cancerous lesions.
We hypothesize that BRCA1- and BRCA2-mediated pancreatic ductal adenocarcinoma progresses through the PanIN route, as seen in both BRCA1 and BRCA2 murine models of pancreatic cancer. We further hypothesize that BRCA1 mutations may enable an additional pre- neoplastic pathway through MCN, and that IPMN may embody yet another pre- neoplastic pathway.
Read the detailed description
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death from malignancy in the United States. Several gene mutations and cancer syndromes have been identified that are found in greater frequency in individuals with PDAC, including the breast ovary cancer syndrome (BRCA1 and BRCA2 mutations). We have recently generated mouse models of pancreatic cancer in which we found that deletions of either BRCA1 or BRCA2 cooperate with K-ras activation and p53 mutations to increase the rate of tumorigenesis via accelerated progression of Pancreatic Intraepithelial Neoplasia (PanIN). However, only BRCA1 deletions were associated with the development of concomitant Mucinous Cystic Neoplasms (MCNs), suggesting potentially distinct pathways for BRCA1- and BRCA2-mediated tumorigenesis in the pancreas. Our primary aim is to determine if germline mutations of BRCA1 and BRCA2 result in different pre-neoplastic pathways to pancreatic cancer, as in our murine model. Genomic DNA will be isolated on normal tissue obtained from patients who underwent pancreatic resection for pancreatic cancer, IPMN or MCN. Tissue will be genotyped for the three most common founder mutations in Ashkenazi Jews. In the cases in which BRCA1 or BRCA2 mutations are found, heterozygote normal and abnormal tissue will be microdissected to look for loss of heterozygosity at the BRCA1 or BRCA2 allele. Our secondary aim is to evaluate the interaction of p53 and Kras with BRCA1 and BRCA2 by sequencing p53 and Kras in PanIN as compared to IPMN and MCN lesions.
- Conditions
- Pancreatic Cancer
- Keywords
- Pancreatic Cancer, Pre-neoplastic lesions, Breast and Ovarian Cancer Syndrome, BRCA1/2, Mouse model for pancreatic cancer
- Medical subject headings
- Pancreatic Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
BRCA1 vs. BRCA2 mutations
The primary aim is to determine if germline mutations of BRCA1 and BRCA2 result in different pre-neoplastic pathways to pancreatic cancer, as seen in our murine model. Genomic DNA will be isolated on normal tissue obtained from patients who underwent pancreatic resection for pancreatic cancer, IPMN or MCN. Tissue will be genotyped for the three most common founder mutations in Ashkenazi Jews. In the cases in which BRCA1 or BRCA2 mutations are found, heterozygote normal and abnormal tissue will be microdissected to look for loss of heterozygosity at the BRCA1 or BRCA2 allele.
Measured: 1 year
Secondary outcomes (1)
Interaction of other cancer genes with BRCA1 and BRCA2
The secondary aim is to evaluate the interaction of p53 and K-ras with BRCA1 and BRCA2 by sequencing p53 and K-ras in PanIN as compared to IPMN and MCN lesions.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2010 (estimated)
- Study startMar 2009
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wendy K. Chung, Columbia University
- Investigators
- Wendy K Chung, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01103128
- Sponsor's protocol ID
- AAAE0097
- Other IDs
- AAAE0097
- Status last verified
- Jul 2012
- First submitted
- 12 Apr 2010
- Last updated
- 23 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BRCA1 and BRCA2 Genetic Mutations in Mucinous Versus Nonmucinous Precursor Lesions of the Pancreas: Validation of a Mouse Model of Pancreatic Carcinogenesis
- ClinicalTrials.gov ID
- NCT01103128
- Acronym / sponsor ID
- AAAE0097
- Conditions
- Pancreatic Cancer
- Keywords
- Pancreatic Cancer, Pre-neoplastic lesions, Breast and Ovarian Cancer Syndrome, BRCA1/2, Mouse model for pancreatic cancer
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 14 Apr 2010 (estimated)
- 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.
The primary aim of this study is to determine if mutations of BRCA1 and BRCA2 result in different precancerous pathways to pancreatic ductal adenocarcinoma (PDAC), as suggested in our validated mouse model. Genomic DNA will be isolated on normal tissue obtained from patients who underwent pancreatic resection for PDAC, intraductal papillary mucinous neoplasm (IPMN) or mucinous cystic neoplasm (MCN). Tissue will be examined for the three most common founder mutations in Ashkenazi Jews. In the cases in which BRCA1 or BRCA2 mutations are found, heterozygote normal and abnormal tissue will be examined to look for mutations in the other BRCA1 or BRCA2 allele. The interaction between other cancer causing genes with BRCA1/2 will also be evaluated by comparing the sequences of the other genes in pre-cancerous lesions.
We hypothesize that BRCA1- and BRCA2-mediated pancreatic ductal adenocarcinoma progresses through the PanIN route, as seen in both BRCA1 and BRCA2 murine models of pancreatic cancer. We further hypothesize that BRCA1 mutations may enable an additional pre- neoplastic pathway through MCN, and that IPMN may embody yet another pre- neoplastic pathway.
Detailed description
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death from malignancy in the United States. Several gene mutations and cancer syndromes have been identified that are found in greater frequency in individuals with PDAC, including the breast ovary cancer syndrome (BRCA1 and BRCA2 mutations). We have recently generated mouse models of pancreatic cancer in which we found that deletions of either BRCA1 or BRCA2 cooperate with K-ras activation and p53 mutations to increase the rate of tumorigenesis via accelerated progression of Pancreatic Intraepithelial Neoplasia (PanIN). However, only BRCA1 deletions were associated with the development of concomitant Mucinous Cystic Neoplasms (MCNs), suggesting potentially distinct pathways for BRCA1- and BRCA2-mediated tumorigenesis in the pancreas. Our primary aim is to determine if germline mutations of BRCA1 and BRCA2 result in different pre-neoplastic pathways to pancreatic cancer, as in our murine model. Genomic DNA will be isolated on normal tissue obtained from patients who underwent pancreatic resection for pancreatic cancer, IPMN or MCN. Tissue will be genotyped for the three most common founder mutations in Ashkenazi Jews. In the cases in which BRCA1 or BRCA2 mutations are found, heterozygote normal and abnormal tissue will be microdissected to look for loss of heterozygosity at the BRCA1 or BRCA2 allele. Our secondary aim is to evaluate the interaction of p53 and Kras with BRCA1 and BRCA2 by sequencing p53 and Kras in PanIN as compared to IPMN and MCN lesions.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All subjects have a tissue-confirmed diagnosis of pancreatic adenocarcinoma, MCN or IPMN and underwent surgical resection for pancreatic adenocarcinoma, MCN or IPMN at Columbia-Presbyterian Medical Center.
Key inclusion criteria (2 listed)
- Tissue-confirmed diagnosis of pancreatic adenocarcinoma, MCN, or IPMN.
- Underwent surgical resection for pancreatic adenocarcinoma, MCN, or IPMN.
Key exclusion criteria (2 listed)
- Unwilling to provide informed consent.
- Under the age of 18.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
BRCA1 vs. BRCA2 mutations
Time frame: 1 year
The primary aim is to determine if germline mutations of BRCA1 and BRCA2 result in different pre-neoplastic pathways to pancreatic cancer, as seen in our murine model. Genomic DNA will be isolated on normal tissue obtained from patients who underwent pancreatic resection for pancreatic cancer, IPMN or MCN. Tissue will be genotyped for the three most common founder mutations in Ashkenazi Jews. In the cases in which BRCA1 or BRCA2 mutations are found, heterozygote normal and abnormal tissue will be microdissected to look for loss of heterozygosity at the BRCA1 or BRCA2 allele.
1 secondary outcome
Interaction of other cancer genes with BRCA1 and BRCA2
Time frame: 1 year
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2015.
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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.
Wendy K Chung, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pancreatic Cancer, run by Columbia University 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 2 inclusion and 2 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 23 Jun 2015. 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.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
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?
BRCA1 vs. BRCA2 mutations (time frame: 1 year). 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 23 Jun 2015.