Exosomes in Rectal Cancer

Exosomal as Correlative Biomarker in Clinical Outcomes in Patients Undergoing Neoadjuvant Chemoradiation Therapy for Rectal Cancer

The primary aims of this study is to characterize exosomal biomarker levels in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation therapy. Compare rates of exosomal expression before during and after chemoradiation therapy with pathologic response rates at the time of APR or LAR. The researchers will also examine the functionality of these exosomes in malignant colonic organoids and mouse models of colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer
• Intervention / Treatment: Diagnostic test: Blood Draw

Detailed Description

All male and female patients, aged 18 and older with a histologically proven diagnosis of rectal adenocarcinoma, treated on this study will receive neo adjuvant chemotherapy (consisting of 5 FU or capecitabine) given concurrently with external beam radiation therapy to a dose of 50.4 Gy in 28 fractions. Radiation treatments will be administered daily, Monday thru Friday. Within one week prior to beginning chemotherapy and radiation treatments, a serum sample will be obtained from each patient. Patients will also have serum samples collected every two weeks during radiation, and on the last day of radiation therapy, as well as at their one month follow up visit after completion of radiation and prior to planned surgery. A final serum sample will be collected within one month after definitive surgery. Each serum sample collected will be less than 50 mL.

The study will involve obtaining serum samples from patients before during and after chemoradiation therapy. These serum samples will be analyzed to determine exosomal biomarker levels, which will be correlated with clinical, imaging, laboratory, and pathologic data obtained from the medical record.

Additional data from the patients' medical records will be collected, including demographic data, clinical information from notes in the medical record, radiology images and reports, results of diagnositic tests, and information from procedure notes and pathology reports.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Leah K Miller, MS; Phone Number: 913-588-3670; Email: lmiller25@kumc.edu

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66190
      • Recruiting
      • University of Kansas Medical Center/ Cancer Center
      • Contact: Mindi TenNapel, PhD; Phone Number: 913-945-9547; Email: mtennapel@kumc.edu
      • Contact: Leah Miller, MS; Phone Number: 913-588-3670; Email: lmiller25@kumc.edu
      • Principal Investigator: Andrew Hoover, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients seen in the Department of Radiation Oncology at The University of Kansas Health System that are over the age of 18 and have a histologically proven diagnosis of rectal adenocarcinoma and will be receiving neoadjuvant chemoradiation therapy before a planned, definitive surgical resection has been performed.

Description

Inclusion Criteria:

• Male and Female Patients aged 18 and older
• histologically proven diagnosis of rectal adenocarcinoma
• will be receiving neoadjuvant chemoradiation therapy prior to a planned definitive surgical resection

Exclusion Criteria:

• Age less than 18.
• Patients who are unable or unwilling to undergo definitive surgery.
• Patients with a prior history of pelvic external beam radiation, brachytherapy, or chemotherapy.
• Patients with a prior history of cancer (excluding non-melanoma skin cancers).
• Patients who are immunocompromised.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm A; All patients enrolled will be placed in Arm A. Serum blood draw samples will be collected as well as additional data from medical records will be collected. This data includes demographic data, clinical information from notes, radiology images and reports, diagnostic test results, and procedure and pathology reports.	Diagnostic test: Blood Draw; Serum samples will be obtained from each patient enrolled

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exosomal Biomarkers Assessment	Characterize exosomal biomarker levels in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation therapy.	up to 10 years after treatment completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exosomal Expression	Compare rates of exosomal expression before during and after chemoradiation therapy with pathologic response rates at the time of APR or LAR. Response rates will be graded based on College of American Pathologists Guidelines on neoadjuvant treatment effect, which consist of a 4 tiered grading system categorizing response to neoadjuvant chemoradiation as "complete", "moderate", "minimal", or "poor". These grades are routinely documented in pathology reports for patients undergoing neoadjuvant chemoradiation for rectal cancer and will be obtained from review of pathology reports in the patient medical records.	up to 10 years after treatment completion
Exosomal Functionality Assessment	Examine the functionality of these exosomes in malignant colonic organoids and mouse models of colorectal cancer.	up to 10 years after treatment completion

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Investigators: Principal Investigator: Andrew Hoover, MD, The University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2018
• Primary Completion (Anticipated): February 1, 2021
• Study Completion (Anticipated): February 1, 2022

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 14, 2019

Study Record Updates

• Last Update Posted (Actual): March 14, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: biomarkers; exosomes; external beam radiation; Low anterior resection; abdominoperineal resection; neoadjuvant chemoradiation therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: Protocol IIT-RE-0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No