Clinical trial NCT00280761: Biomarkers in Patients With Rectal Cancer Undergoing Chemotherapy and Radiation Therapy
Official title: A Biologic Study of Global Gene Expression, NF-Kappa B and p53 in Adenocarcinoma of the Rectum.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the rectum
recurrent rectal cancer
stage II rectal cancer
stage III rectal cancer
stage IV rectal cancer
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-01-23
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients (male, female, any ethnic background) with rectal (inferior margin of the tumor less than 15cms from anal verge by rigid sigmoidoscopy or below the level of S1-2 at operation) or sigmoid-rectal junction carcinomas confirmed by sigmoidoscopy and pathologic diagnosis of biopsy sample.

Brief 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.

Eligibility 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)

PATIENT CHARACTERISTICS:

* Not pregnant

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Activation of NF-kappa B in response to treatment with external beam radiotherapy
timeFrame: 6-8 weeks after chemoradiation
measure: Correlation of NF-kappa B pathway activation with therapeutic outcomes
timeFrame: 6-8 weeks after chemoradiation
Secondary outcomes:
measure: Downstream events induced by NF-kappa B activation
timeFrame: 12 months
measure: Global gene expression profiles at baseline and during chemoradiotherapy
timeFrame: prior to chemoradiation and 72 days post chemoradiation
measure: Correlation of changes in gene expression with patient outcomes
timeFrame: 72 days post chemoradiation
measure: Downstream events related to activation of p53 in response to treatment with radiotherapy
timeFrame: 72 post radiotherapy
measure: Correlation of p53 pathway-mediated events with clinical outcomes
timeFrame: 72 days post chemoradiation
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Hanna Sanoff, MD
role: PRINCIPAL_INVESTIGATOR
References: