NCT00280761

Biomarkers in Patients With Rectal Cancer Undergoing Chemotherapy and Radiation Therapy

A Biologic Study of Global Gene Expression, NF-Kappa B and p53 in Adenocarcinoma of the Rectum.

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 47 (actual)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors understand how patients respond to treatment. PURPOSE: This clinical trial is studying biomarkers in patients with rectal cancer undergoing chemotherapy and radiation therapy.

Detailed description

OBJECTIVES: Primary * Observe whether NF-kappa B is activated in response to treatment with external beam radiotherapy. * Correlate NF-kappa B pathway activation (presumed to be anti-apoptotic in nature) with therapeutic outcomes (as measured by rate of pathologic complete response or downstaging by endoscopic ultrasound \[EUS\]). Secondary * Study downstream events induced by NF-kappa B activation. * Determine global gene expression profiles at baseline and during chemoradiotherapy. * Correlate changes in gene expression (compared with the baseline gene expression pattern) induced by a single dose of external beam radiotherapy with patient outcomes (as measured by pathologic response rate or downstaging by EUS). * Study downstream events related to activation of p53 in response to treatment with radiotherapy. * Correlate p53 pathway-mediated events with clinical outcomes. OUTLINE: Patients receive fluorouracil or capecitabine and undergo radiotherapy and surgery per standard care. Patients undergo tumor pinch biopsies at baseline and on days 1 and 2 of chemoradiotherapy. At the time of final surgical resection, a portion of the remaining rectal tumor will be liquid nitrogen banked. Patients not deemed surgical candidates are evaluated by transrectal ultrasound 6-8 weeks after completion of chemoradiotherapy to assess ultrasound response (downstaging versus no downstaging). Tumor tissue samples are analyzed for NF-kappa B pathway activation; downstream events induced by NF-kappa B activation; changes in global gene expression; p53 function; apoptosis; and mRNA expression. Laboratory techniques used include tissue microarray, ELISA, RNase protection assay, fluorescence semi-quantitative PCR, TUNEL, IHC, and cDNA microarray analysis. If normal tissue from biopsies is not available, whole blood may be collected at any point while patient remains on study for correlative analysis or research related to rectal cancer.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
DRUG	capecitabine	Capecitabine administration (where deemed appropriate by the treating medical oncologist) will commence on the second day of radiotherapy after the 24-hour biopsy has been performed. Dosing will be per current standard of care at the discretion of the treating Medical, Radiation and Surgical Oncologist
DRUG	5-fluorouracil	Administration of 5-fluorouracil (where deemed appropriate by the treating medical oncologist) will commence on the second day of radiotherapy after the 24-hour biopsy has been performed. Dosing and dose modification will be per current standard of care at the discretion of the treating Medical, Radiation and Surgical Oncologist.
PROCEDURE	Surgical Resection	Surgery will occur approximately 2-6 weeks after chemoradiation depending on clinical factors (i.e. resectability, presence or absence of metastatic disease).
RADIATION	Radiation therapy	Dosing and dose modification will be per current standard of care at the discretion of the treating Radiation Oncologist.

Timeline

• Start date: 2003-12-01
• Primary completion: 2021-09-19
• Completion: 2021-09-19
• First posted: 2006-01-23
• Last updated: 2022-08-11

Locations

1 site across 1 country: United States