Ohio Colorectal Cancer Prevention Initiative

Colorectal Cancer Clinical Trial

— OCCPI  

Official title:

Ohio Colorectal Cancer Prevention Initiative: Universal Screening for Lynch Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01850654
• Other study ID #: OSU-12170
• Status: Completed
• Phase: N/A
• Start date: December 26, 2012
• Est. completion date: January 2, 2018

Study information

• Verified date: June 2018
• Source: Ohio State University Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the Ohio Colorectal Cancer Prevention Initiative (OCCPI) is to reduce morbidity and mortality due to colorectal cancer (CRC) in the state of Ohio. By identifying individuals at high-risk for CRC (genetically predisposed) and providing screening recommendations for cancer risk reduction, the OCCPI will understand how to increase length of life and quality of life for those diagnosed with CRC in Ohio, as well as to better prevent CRC in others in Ohio.

Participants will have free tumor screening for Lynch syndrome, and may be eligible for free genetic testing and free genetic counseling as part of this study.

Description:

Lynch Syndrome:

Lynch syndrome (LS), previously known as "hereditary non-polyposis colorectal cancer", is a hereditary cancer syndrome that causes the majority of hereditary CRC and approximately 3% of all CRC. LS significantly increases the risk for an individual to develop CRC during their lifetime. Individuals with LS also have an increased risk to develop extracolonic cancers, including endometrial, gastric, ovarian, upper urinary tract, small bowel, biliary tract, CNS, and certain types of skin cancer. Tumor studies, including microsatellite instability (MSI) testing and immunohistochemical (IHC) analysis, provide information regarding characteristic features of LS-associated tumors and can help target genetic testing. Given the hereditary nature of this syndrome, screening all patients who are newly diagnosed with CRC for LS can identify additional individuals who are at high-risk of developing cancer.

Study Aims:

By developing a CRC research infrastructure within the state of Ohio, the OCCPI will achieve the following specific aims:

• Establish and implement a statewide universal screening protocol for LS.

• Elucidate the prevalence of hereditary CRC in Ohio.

• Provide screening recommendations for high-risk individuals with CRC and their families, as well as local access to genetic counseling.

• Create a CRC biorepository for future research on the etiology of CRC from the leftover samples of the CRC patients, as well as samples from their relatives.

With the successful implementation of the OCCPI, knowledge will be gained that will facilitate the adoption of a universal screening protocol for LS in Ohio and the creation of a statewide CRC biorepository to be used for additional studies on cancer risks, prevention, screening, treatment and survivorship.

Study Procedures for CRC and EC participants:

• You will be asked to donate 2-3 tablespoons of blood.

• A small piece of your colorectal or endometrial tumor will be obtained from the hospital where you had your surgery.

• You will be asked to contribute your leftover samples (tumor and blood) to the OCCPI biorepository (sample bank) for help with future research. Additionally, CRC participants will be asked to donate a saliva sample to the OCCPI biorepository. The samples will be kept securely in a lab at OSU. Before your samples can be used for research, the people doing the research must get specific approval from the OCCPI Steering Committee and possibly the Institutional Review Board (IRB) of OSU. The IRB is responsible for protecting the participants involved in research studies and making sure all research is done in a safe and ethical manner.

• You will be asked to complete a questionnaire which will ask about your age, medical history, family history, lifestyle factors and environmental exposures. It should take about one hour to complete the questionnaire and you can complete it from home.

• We will test your tumor for features of LS (MSI, IHC, methylation).

• For CRC patients: if your tumor shows features of LS OR you were diagnosed under age 50 OR you have a family history of CRC or endometrial cancer OR you have synchronous or metachronous CRC or endometrial cancer, we will test your blood for the genes that cause LS, as well as other genes that can cause hereditary cancer.

• For endometrial cancer patients: if your tumor shows features of LS, we will test your blood for the genes that cause LS, as well as other genes that can cause hereditary cancer.

• Some patients may have tumor genetic testing.

• If you are found to have LS or another type of hereditary cancer, you will be offered free genetic counseling.

• If you are found to have LS, your at-risk relatives will be offered free genetic counseling and genetic testing.

Study Procedures for first-degree relatives (FDR) of the CRC participants:

The FDRs of all of the CRC study participants will be given the opportunity to contribute to the biorepository for future research.

• Family Member Consent for Contact forms will be provided to the CRC participant at the time of their enrollment for them to distribute to all of their FDRs (parents, siblings and adult children ≥ 25 years). The FDRs will mail the signed form to OSU.

• After obtaining permission to contact the FDRs, OSU will mail them the biorepository consent form and saliva kit to return to the OCCPI biorepository.

• The FDRs of the CRC study participants will also be invited to complete the baseline questionnaire.

Length of study:

• The LS tumor screening portion of the OCCPI will take 1-4 months.

• If applicable, genetic testing results should be ready in an additional 3-6 months.

• Overall, your participation in the LS screening portion of the OCCPI is expected to take about 1 year. Most of this time will be spent waiting for results. Your active involvement will take about 15 minutes on the day that you provide consent and about 60 minutes when you complete the questionnaire from home.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3470
• Est. completion date: January 2, 2018
• Est. primary completion date: January 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Newly diagnosed with colorectal adenocarcinoma (all stages) and have a resection at any hospital in Ohio between 1/1/2013 and 12/31/2016.

• For individuals who have neoadjuvant treatment and show a complete response at resection, the tumor screening will be attempted on their original biopsy (even if it occurred in 2012) as long as their resection occurred between 1/1/2013 and 12/31/2016.

• Many individuals with stage IV CRC will not have a resection; therefore, the tumor screening will be attempted on their original colon biopsy as long as their primary diagnosis occurred between 1/1/2013 and 12/31/2016. If only metastatic CRC is available on a biopsy (liver or lymph node metastases), tumor screening will be attempted on the metastatic tissue.

2. Newly diagnosed with endometrial cancer (any histology except sarcoma) and have a resection between 1/1/2013 and 12/31/2016 at OSU only.

3. All at-risk relatives of the participants found to have LS.

4. First-degree relatives (parents, siblings and adult children = 25 years of age) of the CRC participants who do not have LS.

Exclusion Criteria:

1. Prisoners.

2. Individuals who are under the age of 18.

3. Individuals must have a primary colorectal or endometrial cancer, not a recurrence of a previous colorectal or endometrial cancer.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Colorectal Neoplasms, Hereditary Nonpolyposis
• Lynch Syndrome
• Syndrome

Intervention

Genetic:
• LS tumor screening
All participants with CRC or EC will have LS tumor screening (MSI, IHC, methylation if applicable).
• Genetic testing
Next-generation sequencing panel of several genes that increase the risk for hereditary cancers including the LS genes (MLH1, MSH2, MSH6, PMS2, EPCAM), polyposis genes (MUTYH, APC), and others. The following study participants will have free genetic testing: CRC and EC study participants with unmethylated MSI-high (MSI-H) tumors CRC and EC study participants with microsatellite stable (MSS) or MSI-low (MSI-L) tumors who have abnormal IHC results and they do not have methylation of the MLH1 promoter CRC study participants diagnosed with CRC <50 years, regardless of tumor studies or family history CRC study participants diagnosed with CRC = 50 years with a FDR with CRC or EC OR synchronous or metachronous CRC or EC throughout their life, regardless of tumor studies. At-risk relatives of the individuals found to have LS are eligible for free single site genetic testing.

Behavioral:
• Genetic Counseling
The participants found to have LS or another type of hereditary cancer will have free genetic counseling. At-risk relatives of the individuals found to have LS are eligible for free genetic counseling.

Other:
• Biorepository
The biorepository is an optional part of the OCCPI. CRC and EC participants will contribute leftover tumor and blood samples, as well as a saliva sample. FDR of the CRC participants will contribute a saliva sample. The at-risk relatives of those found to have LS will contribute blood and saliva samples.

Behavioral:
• Questionnaire

Locations

Country	Name	City	State
United States	Akron City/St. Thomas Hospital (Summa Health System)	Akron	Ohio
United States	Akron General Medical Center	Akron	Ohio
United States	Summa Barberton (Summa Health System)	Barberton	Ohio
United States	Mercy Clermont	Batavia	Ohio
United States	Aultman Hospital	Canton	Ohio
United States	Mercy Medical Center	Canton	Ohio
United States	Adena Health System	Chillicothe	Ohio
United States	Bethesda North Hospital (TriHealth)	Cincinnati	Ohio
United States	Good Samaritan Hospital (TriHealth)	Cincinnati	Ohio
United States	Mercy Anderson	Cincinnati	Ohio
United States	Mercy West	Cincinnati	Ohio
United States	The Christ Hospital	Cincinnati	Ohio
United States	The Jewish Hospital	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Fairview Hospital	Cleveland	Ohio
United States	MetroHealth	Cleveland	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Summa Western Reserve (Summa Health System)	Cuyahoga Falls	Ohio
United States	Good Samaritan Hospital Dayton	Dayton	Ohio
United States	Kettering Medical Center	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Wright-Patterson Medical Center	Dayton	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Mercy Fairfield	Fairfield	Ohio
United States	Blanchard Valley Health System	Findlay	Ohio
United States	Wayne Healthcare	Greenville	Ohio
United States	Fairfield Medical Center	Lancaster	Ohio
United States	St. Rita's Medical Center	Lima	Ohio
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Marion General Hospital	Marion	Ohio
United States	St. Luke's Hospital (ProMedica)	Maumee	Ohio
United States	Toledo Clinic Cancer Center	Maumee	Ohio
United States	Hillcrest Hospital	Mayfield Heights	Ohio
United States	Atrium Medical Center	Middletown	Ohio
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Licking Memorial Hospital	Newark	Ohio
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Robinson Memorial (Summa Health System)	Ravenna	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Flower Hospital (ProMedica Health System)	Sylvania	Ohio
United States	Toledo Hospital (Promedica Health System)	Toledo	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	South Pointe Hospital	Warrensville Heights	Ohio
United States	Mount Carmel St. Ann's Hospital	Westerville	Ohio
United States	Genesis Cancer Care Center (Genesis Healthcare System)	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

References & Publications (4)

Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med. 2009 Jan;11(1):35-41. doi: 10.1097/GIM.0b013e31818fa2ff. — View Citation

Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Clendenning M, Sotamaa K, Prior T, Westman JA, Panescu J, Fix D, Lockman J, LaJeunesse J, Comeras I, de la Chapelle A. Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol. 2008 Dec 10;26(35):5783-8. doi: 10.1200/JCO.2008.17.5950. Epub 2008 Sep 22. — View Citation

Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005 May 5;352(18):1851-60. — View Citation

Palomaki GE, McClain MR, Melillo S, Hampel HL, Thibodeau SN. EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med. 2009 Jan;11(1):42-65. doi: 10.1097/GIM.0b013e31818fa2db. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the Incidence of Hereditary Cancer Syndromes among Newly Diagnosed Colorectal Cancer Patients	Through tumor testing for Lynch syndrome and follow-up genetic testing for all patients with abnormal tumor testing and select patients with normal tumor testing (those diagnosed under age 50 and those at or over age 50 with a first degree relative with colorectal or endometrial cancer or synchronous or metachronous colon or endometrial cancer).	36 months (initial assessment)

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