Biomarkers in Patients With Rectal Cancer Undergoing Chemotherapy and Radiation Therapy

NCT ID: NCT00280761

Last Updated: 2022-08-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 47 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2003-12-31
• Study Completion Date: 2021-09-19

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.

Conditions

Colorectal Cancer

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

1

Single Arm Trial

capecitabine

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Surgical Resection

Intervention Type: PROCEDURE

Surgery will occur approximately 2-6 weeks after chemoradiation depending on clinical factors (i.e. resectability, presence or absence of metastatic disease).

Radiation therapy

Intervention Type: RADIATION

Dosing and dose modification will be per current standard of care at the discretion of the treating Radiation Oncologist.

Interventions

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

Surgical Resection

Surgery will occur approximately 2-6 weeks after chemoradiation depending on clinical factors (i.e. resectability, presence or absence of metastatic disease).

Intervention Type: PROCEDURE

Radiation therapy

Dosing and dose modification will be per current standard of care at the discretion of the treating Radiation Oncologist.

Intervention Type: RADIATION

Other Intervention Names

Xeloda; 5-FU; EBRT - External Beam Radiation Therapy

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hanna Sanoff, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

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

Chapel Hill, North Carolina, United States

Countries

United States

Related Links

http://www.unclineberger.org/

web address for UNC Lineberger Comprehensive Cancer Center

http://www.cancer.gov/

web address for the National Cancer Institute (NCI)

Other Identifiers

P30CA016086

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000561688

Identifier Type: OTHER

Identifier Source: secondary_id

LCCC 0216

Identifier Type: -

Identifier Source: org_study_id