Biomarkers in Patients With Rectal Cancer Undergoing Chemotherapy and Radiation Therapy

UNC Lineberger Comprehensive Cancer Center

Status

Completed

Conditions

Colorectal Cancer

Treatments

Procedure: Surgical Resection

Drug: 5-fluorouracil

Drug: capecitabine

Radiation: Radiation therapy

Study type

Observational

Funder types

Other

NIH

Identifiers

NCT00280761

LCCC 0216

CDR0000561688 (Other Identifier)

P30CA016086 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

47 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

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 examination
- 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)