Trial Information

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

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.