Publications & Clinical Trials

Hereditary and common familial colorectal cancer: evidence for colorectal screening.
Samadder NJ, Jasperson K, Burt RW.
Dig Dis Sci. 2015 Mar;60(3):734-47.


APC promoter 1B deletion in seven American families with familial adenomatous polyposis.
Snow AK, Tuohy TM, Sargent NR, Smith LJ, Burt RW, Neklason DW.
Clin Genet. 2014 Sep 19. doi: 10.1111/cge.12503. [Epub ahead of print]


Increased risk of colorectal neoplasia among family members of patients with colorectal cancer: a population-based study in Utah.
Samadder NJ, Curtin K, Tuohy TM, Rowe KG, Mineau GP, Smith KR, Pimentel R, Wong J, Boucher K, Burt RW.
Gastroenterology. 2014 Oct;147(4):814-821


Epidemiology and Familial Risk of Synchronous and Metachronous Colorectal Cancer: A Population-Based Study in Utah.
Samadder NJ, Curtin K, Wong J, Tuohy TM, Mineau GP, Smith KR, Pimentel R, Pappas L, Boucher K, Garrido-Laguna I, Provenzale D, Burt RW
Clin Gastroenterol Hepatol. 2014 Apr 24. pii: S1542-3565(14)00605-3


Characteristics of missed or interval colorectal cancer and patient survival: a population-based study.
Samadder NJ, Curtin K, Tuohy TM, Pappas L, Boucher K, Provenzale D, Rowe KG, Mineau GP, Smith K, Pimentel R, Kirchhoff AC, Burt RW.
Gastroenterology. 2014 Apr;146(4):950-60.


Risk of colorectal cancer and adenomas in the families of patients with adenomas: a population-based study in Utah.
Tuohy TM, Rowe KG, Mineau GP, Pimentel R, Burt RW, Samadder NJ.
Cancer. 2014 Jan 1;120(1):35-42.


RNA sequencing of sessile serrated colon polyps identifies differentially expressed genes and immunohistochemical markers.
Delker DA, McGettigan BM, Kanth P, Pop S, Neklason DW, Bronner MP, Burt RW, Hagedorn CH.
PLoS One. 2014 Feb 12;9(2):e88367.


Activating mutation in MET oncogene in familial colorectal cancer.
Neklason DW, Done MW, Sargent NR, Schwartz AG, Anton-Culver H, Griffin CA, Ahnen DJ, Schildkraut JM, Tomlinson GE, Strong LC, Miller AR, Stopfer JE, Burt RW.
BMC Cancer. 2011 Oct 4;11:424.


Colorectal adenomas and cancer link to chromosome 13q22.1-13q31.3 in a large family with excess colorectal cancer.
Neklason DW, Tuohy TM, Stevens J, Otterud B, Baird L, Kerber RA, Samowitz WS, Kuwada SK, Leppert MF, Burt RW.
J Med Genet. 2010 Oct;47(10):692-9.


Hereditary and familial colon cancer.
Jasperson KW, Tuohy TM, Neklason DW, Burt RW.
Gastroenterology. 2010 Jun;138(6):2044-58. Review.


Population-based family history-specific risks for colorectal cancer: a constellation approach.
Taylor DP, Burt RW, Williams MS, Haug PJ, Cannon-Albright LA.
Gastroenterology. 2010 Mar;138(3):877-85.


Large intron 14 rearrangement in APC results in splice defect and attenuated FAP.
Tuohy TM, Done MW, Lewandowski MS, Shires PM, Saraiya DS, Huang SC, Neklason DW, Burt RW.
Hum Genet. 2010 Mar;127(3):359-69.


Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis.
Neklason DW, Kerber RA, Nilson DB, Anton-Culver H, Schwartz AG, Griffin CA, Lowery JT, Schildkraut JM, Evans JP, Tomlinson GE, Strong LC, Miller AR, Stopfer JE, Finkelstein DM, Nadkarni PM, Kasten CH, Mineau GP, Burt RW.
Cancer Res. 2008 Nov 1;68(21):8993-7.


Colonic adenoma risk in familial colorectal cancer--a study of six extended kindreds.
Neklason DW, Thorpe BL, Ferrandez A, Tumbapura A, Boucher K, Garibotti G, Kerber RA, Solomon CH, Samowitz WS, Fang JC, Mineau GP, Leppert MF, Burt RW, Kuwada SK.
Am J Gastroenterol. 2008 Oct;103(10):2577-84.


American founder mutation for attenuated familial adenomatous polyposis.
Neklason DW, Stevens J, Boucher KM, Kerber RA, Matsunami N, Barlow J, Mineau G, Leppert MF, Burt RW.
Clin Gastroenterol Hepatol. 2008 Jan;6(1):46-52.


Frequency of familial colon cancer and hereditary nonpolyposis colorectal cancer (Lynch syndrome) in a large population database.
Kerber RA, Neklason DW, Samowitz WS, Burt RW.
Fam Cancer. 2005;4(3):239-44.


Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis.
Burt RW, Leppert MF, Slattery ML, Samowitz WS, Spirio LN, Kerber RA, Kuwada SK, Neklason DW, Disario JA, Lyon E, Hughes JP, Chey WY, White RL.
Gastroenterology. 2004 Aug;127(2):444-51.


The key to finding new and better treatments for cancer lies in research. The Huntsman Cancer Institute (HCI) Clinical Trials Office (CTO) continually develops new approaches to help cancer patients live longer and better lives. Patient participation in clinical trials is an essential factor in this process.
High Risk Cancer Research Clinics and Studies provide information for investigations into the genetics and inheritance of cancer. The clinics provide education, and in some cases cancer screening services, for eligible people with an increased risk of developing cancer.

These publications can be downloaded for personal use and are not intended for redistribution.

Clinical Trials

Protocol Summary

Protocol No. 39278 
Principal Investigator: Samadder, Jewel (Niloy)
Phase: II (Cancer Prevention)
Age Group: Adult
Secondary Protocol No. PPG- NIH Trial

Title
Genetic Events Leading to APC-Dependent Colon Cancer in High-Risk Families; a Clinical Trial of COX and EGFR Inhibition in Familial Polyposis Patients

Objective
This will be a single-center, phase-II, six-month-long, placebo-controlled, double blinded, randomized trial of the EGFR inhibitor erlotinib (Tarceva) and the COX inhibitor sulindac in patients with familial adenomatous polyposis (FAP) or attenuated FAP. FAP is an autosomal dominant inherited colon cancer predisposition with a 100% risk of colon cancer in the absence of preventive care (endsosopy and surgery). Efficacious chemoprevention for duodenal adenomas is an unmet clinical need in FAP patients that would reduce the morbidity from duodenectomy and risk of duodenal adenocarcinoma. Currently the only FDA-approved chemopreventive agent is celecoxib which results in a modest reduction of duodenal and colorectal polyps and is associated with cardiac toxicity at effective doses. If it can be shown that combinatorial inhibition of COX-2 and EGFR activity leads to successful regression in duodenal adenomatous polyps in FAP, it could be used as an effective chemopreventive regimen in FAP patients with duodenal adenomas or who have undergone surgical resection of duodenal adenomas or have many rectal adenomas. FAP and AFAP pateints will be screened by endoscopy for presence of 5 or more duodenal polyps, then randomized to either A) erlotinib at 75 mg/day and sulindac at 150 mg/day or B) placebo for 6 months. The endpoint will be endoscopy at 6 months.

Primary Aim : To determine if the combination of sulindac and erlotinib causes a significant regression of duodenal and colorectal adenomas in FAP and attenuated FAP patients.

Secondary :

1. Measure changes in COX-2 expression, EGFR phosphorylation, MEK1 phosphorylation, AKT phosphorylation, Ki-67 expression and/or cyclin D1 expression in intestinal polyps and normal intestinal mucosa with treatment.

2. Determine ß-catenin localization in adenomatous intestinal polyps with or without oncogenic KRAS mutations.

Key Eligibility
See attached PDF

Applicable Disease Sites: Genitourinary

Participating Institutions: Huntsman Cancer Institute

Status: Open

Other Attachments: Eligibility Criteria.pdf

Mary Beckerle

Randall Burt, MD
Co-Principal Investigator

Cancer Center Bio
Deborah Neklason

Deborah Neklason, PhD
Co-Principal Investigator

Cancer Center Bio

Contact Us

Randall Burt, MD
Co-Principal Investigator
Email: randall.burt@hci.utah.edu

Deborah Neklason, PhD
Co-Principal Investigator
Email: deb.neklason@hci.utah.edu

Kelly Smith
Administrative Contact
Phone: 801-213-5614
Lab Phone: 801-585-2066