Genetic Mutations in Blood and Tissue Samples in Predicting Response to Treatment in Patients With Locally Advanced Rectal Cancer Undergoing Chemoradiation

June 30, 2023 updated by: Fox Chase Cancer Center

Assessing Intratumoral Heterogeneity and Chemoradiation Response in Locally Advanced Rectal Cancer Utilizing Sequencing and PET/CT

This research trial studies genetic mutations in blood and tissue samples to see if they can be used to predict treatment response in patients with locally advanced rectal cancer undergoing chemoradiation. Studying samples of blood and tumor tissue in the laboratory from patients with cancer may help doctors learn more about genetic mutations or changes that occur in deoxyribonucleic acid (DNA) and help doctors understand how patients respond to treatment.

Study Overview

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the tumor-specific mutation(s) detected using the CancerCode™ mutation panel as a predictor of pathologic response to chemoradiation for patients with rectal adenocarcinoma undergoing chemoradiation.

SECONDARY OBJECTIVES:

I. To assess the feasibility of utilizing biopsy specimens from locally advanced rectal adenocarcinoma to perform CancerCode™ mutation panel genetic testing.

II. To assess disease-free survival (DFS) and overall survival (OS) of patients treated on study.

III. To collect pilot data regarding the clonal heterogeneity of rectal adenocarcinoma, and the relationship of this heterogeneity with treatment response.

IV. To evaluate the treatment response utilizing multiple fludeoxyglucose F 18-positron emission tomography (FDG-PET) parameters including heterogeneity and textural features as an exploratory study.

OUTLINE:

Patients undergo collection of blood and tissue samples for analysis via sequencing.

After completion of study, patients are followed up every 3 months for 3 years.

Study Type

Observational

Enrollment (Actual)

43

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Outpatient clinic

Description

Inclusion Criteria:

  • Locally advanced rectal adenocarcinoma: T3-4NanyM0 or TanyN1-2M0
  • Radiologically measurable or clinically evaluable disease
  • Provide informed written consent
  • Willing to return to enrolling medical site for all study assessments

Exclusion Criteria:

  • Chemotherapy within 5 years prior to registration; (hormonal therapy is allowable if the disease free interval is >= 5 years)
  • Any prior pelvic radiation
  • Patients who are at high risk of complications from temporarily discontinuing anticoagulation for rectal cancer biopsies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Ancillary-Correlative (genetic mutation analysis)
Patients undergo collection of blood and tissue samples for analysis via sequencing.
Correlative studies
Correlative studies
Other Names:
  • cytologic sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of the randomly chosen samples that are successfully sequenced
Time Frame: Up to 3 years
If >= 90% of the specimens (at least 72 out of 80) are useable, the method will be considered feasible.
Up to 3 years
Tumor response measured using the tumor regression grading system
Time Frame: Up to 3 years
Whether mutations in any gene on the CancerCode mutation panel are associated with tumor response will be assessed. In each sample, the presence or absence of mutations (0/1) for each gene on the panel will be evaluated. Each gene will be tested separately for its association with tumor response using a two-sample Mann-Whitney-Wilcoxon test with a type-I error of 0.05 for a two-sided test.
Up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor heterogeneity in patients with partial response to radiation
Time Frame: Up to 3 years
Whether there are differences in the mutation profiles in the 4 tumor samples will be assessed, with differences being considered evidence of possible heterogeneity.
Up to 3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: Up to 3 years
PFS will be calculated using the methods of Kaplan and Meier. If promising mutations are identified, survival between mutation positive and negative patients will be compared using the log-rank test.
Up to 3 years
Overall survival
Time Frame: Up to 3 years
OS will be calculated using the methods of Kaplan and Meier. If promising mutations are identified, survival between mutation positive and negative patients will be compared using the log-rank test.
Up to 3 years
Changes in mutation profiles
Time Frame: Baseline to up to 3 years
Any differences between pre- and post- test results (a different mutation status for any gene on the panel) will be considered evidence of a change. The overall proportion of patients exhibiting pre-post differences will be characterized, and particular genes of interest may be tested individually with an exact test of marginal homogeneity.
Baseline to up to 3 years
PET-computed tomography parameters
Time Frame: Up to 3 years
Maximum standardized uptake value will be calculated, as well as textural measures such as coarseness, busyness, contrast, and complexity. The Mann-Whitney-Wilcoxon tests will be used to examine association between image measures and response. Image measures before and after radiation using the Wilcoxon signed rank test for paired data will be compared and differences in textural measures across tumor grades 0-3 will be assessed using the Kruskal-Wallis test. Associations between textural measures and tumor mutation profiles will be explored, also using non-parametric tests.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Joshua Meyer, Fox Chase Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2014

Primary Completion (Actual)

April 8, 2022

Study Completion (Estimated)

April 1, 2024

Study Registration Dates

First Submitted

May 6, 2014

First Submitted That Met QC Criteria

May 6, 2014

First Posted (Estimated)

May 7, 2014

Study Record Updates

Last Update Posted (Actual)

July 3, 2023

Last Update Submitted That Met QC Criteria

June 30, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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