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NCT Number: NCT02132858

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

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.

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Key information

Conditions

Mucinous Adenocarcinoma of the Rectum Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases Rectal Neoplasms Recurrent Rectal Cancer 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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Cytology Specimen Collection Procedure

Other

Correlative studies

Other names: cytologic sampling

laboratory biomarker analysis

Other

Correlative studies

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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.

Other outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

Sponsors and collaborators

Lead sponsor

Fox Chase Cancer Center

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

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

Important dates

Study start
2014
Primary completion
2022
Study completion
2022
First posted
May 7, 2014
Registry last updated
May 2, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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