Biomarkers in Patients With Rectal Cancer Undergoing Chemotherapy and Radiation Therapy

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00280761
• Other study ID #: LCCC 0216
• Secondary ID: P30CA016086CDR00
• Status: Completed
• Start date: December 2003
• Est. completion date: September 19, 2021

Study information

• Verified date: August 2022
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: September 19, 2021
• Est. primary completion date: September 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Rectal Neoplasms

Intervention

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
• 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.

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Activation of NF-kappa B in response to treatment with external beam radiotherapy		6-8 weeks after chemoradiation
Primary	Correlation of NF-kappa B pathway activation with therapeutic outcomes		6-8 weeks after chemoradiation
Secondary	Downstream events induced by NF-kappa B activation		12 months
Secondary	Global gene expression profiles at baseline and during chemoradiotherapy		prior to chemoradiation and 72 days post chemoradiation
Secondary	Correlation of changes in gene expression with patient outcomes		72 days post chemoradiation
Secondary	Downstream events related to activation of p53 in response to treatment with radiotherapy		72 post radiotherapy
Secondary	Correlation of p53 pathway-mediated events with clinical outcomes		72 days post chemoradiation

External Links

•   web address for the National Cancer Institute (NCI)
•   web address for UNC Lineberger Comprehensive Cancer Center