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

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

• Status: Completed
• Conditions: Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer; Recurrent Rectal Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: cytology specimen collection procedure

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

Study Locations

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

Participation Criteria

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

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ancillary-Correlative (genetic mutation analysis); Patients undergo collection of blood and tissue samples for analysis via sequencing.	Other: laboratory biomarker analysis; Correlative studies; Other: cytology specimen collection procedure; 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	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	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	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)	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	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	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	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

• Sponsor: Fox Chase Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Joshua Meyer, Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): April 8, 2022
• Study Completion (Actual): October 1, 2022

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): May 2, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Adenocarcinoma; Rectal Neoplasms; Cystadenocarcinoma; Adenocarcinoma, Mucinous
• Other Study ID Numbers: CGI-066 (Other Identifier: Fox Chase Cancer Center); P30CA006927 (U.S. NIH Grant/Contract); NCI-2014-00719 (Registry Identifier: CTRP (Clinical Trial Reporting Program))