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

Completed

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

• Registration Number: NCT02132858
• Lead Sponsor: Fox Chase Cancer Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2014-05-06
• Study First Submitted QC: 2014-05-06
• Study First Posted: 2014-05-07
• Study Start: 2014-07
• Primary Completion: 2022-04-08
• Study Completion: 2022-10
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-01
• Last Update Posted: 2024-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ancillary-Correlative (genetic mutation analysis)	laboratory biomarker analysis	Patients undergo collection of blood and tissue samples for analysis via sequencing.
Ancillary-Correlative (genetic mutation analysis)	cytology specimen collection procedure	Patients undergo collection of blood and tissue samples for analysis via sequencing.

Primary Outcome Measures

Name	Time	Method
Proportion of the randomly chosen samples that are successfully sequenced	Up to 3 years	If \>= 90% of the specimens (at least 72 out of 80) are useable, the method will be considered feasible.
Tumor response measured using the tumor regression grading system	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.

Secondary Outcome Measures

Name	Time	Method
Tumor heterogeneity in patients with partial response to radiation	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.

Trial Locations

Locations (1)

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States