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

18 Years
Open (Enrolling)
Colorectal Cancer

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Trial Information

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



- Observe whether NF-kappa B is activated in response to treatment with external beam

- 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]).


- 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

- 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

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

Inclusion Criteria


- Must have rectal or sigmoid-rectal junction adenocarcinoma confirmed by sigmoidoscopy
and pathologic diagnosis of biopsy sample

- Inferior margin of the tumor less than 15 cm from anal verge by rigid
sigmoidoscopy or below the level of S1-2 at surgery

- Candidate for chemotherapy and radiotherapy, as defined by any of the following:

- Tumor staged as T3 or N1-2 by rectal sonography

- Tumor occupying > 40% of circumference of rectum

- Tumor fixed to extra colonic structures as determined by digital rectal

- Tumor < 5 cm from sphincter mechanism

- Patient has inoperable disease and is being treated for palliation

- Pelvic or anastomotic recurrences of previously resected rectal cancer

- Planning to undergo chemotherapy and radiotherapy

- No sigmoid carcinoma (carcinoma proximal to the pelvic peritoneal reflection)


- Not pregnant


- See Disease Characteristics

Type of Study:


Study Design:

Observational Model: Case-Only, Time Perspective: Prospective

Outcome Measure:

Activation of NF-kappa B in response to treatment with external beam radiotherapy

Outcome Time Frame:

6-8 weeks after chemoradiation

Safety Issue:


Principal Investigator

Bert H. O'Neil, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:

LCCC 0216



Start Date:

December 2003

Completion Date:

December 2015

Related Keywords:

  • Colorectal Cancer
  • adenocarcinoma of the rectum
  • recurrent rectal cancer
  • stage II rectal cancer
  • stage III rectal cancer
  • stage IV rectal cancer
  • Adenocarcinoma
  • Rectal Neoplasms
  • Colorectal Neoplasms



Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill, North Carolina  27599-7570