Biomarkers in Patients With Rectal Cancer Undergoing Chemotherapy and Radiation Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by UNC Lineberger Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00280761
First received: January 19, 2006
Last updated: March 22, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention
Colorectal Cancer
Drug: capecitabine
Drug: 5-fluorouracil
Procedure: Surgical Resection
Radiation: Radiation therapy

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Biologic Study of Global Gene Expression, NF-Kappa B and p53 in Adenocarcinoma of the Rectum.

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Activation of NF-kappa B in response to treatment with external beam radiotherapy [ Time Frame: 6-8 weeks after chemoradiation ] [ Designated as safety issue: No ]
  • Correlation of NF-kappa B pathway activation with therapeutic outcomes [ Time Frame: 6-8 weeks after chemoradiation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Downstream events induced by NF-kappa B activation [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Global gene expression profiles at baseline and during chemoradiotherapy [ Time Frame: prior to chemoradiation and 72 days post chemoradiation ] [ Designated as safety issue: No ]
  • Correlation of changes in gene expression with patient outcomes [ Time Frame: 72 days post chemoradiation ] [ Designated as safety issue: No ]
  • Downstream events related to activation of p53 in response to treatment with radiotherapy [ Time Frame: 72 post radiotherapy ] [ Designated as safety issue: No ]
  • Correlation of p53 pathway-mediated events with clinical outcomes [ Time Frame: 72 days post chemoradiation ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Adenocarcinoma of the Rectum


Estimated Enrollment: 60
Study Start Date: December 2003
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
Single Arm Trial
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
Other Name: Xeloda
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.
Other Name: 5-FU
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.
Other Name: EBRT - External Beam 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00280761

Locations
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7295
Contact: Bert O'Neil, MD    919-966-4432      
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Bert H. O'Neil, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00280761     History of Changes
Other Study ID Numbers: LCCC 0216, P30CA016086, CDR0000561688
Study First Received: January 19, 2006
Last Updated: March 22, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
adenocarcinoma of the rectum
recurrent rectal cancer
stage II rectal cancer
stage III rectal cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Adenocarcinoma
Rectal Neoplasms
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Fluorouracil
Capecitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 14, 2014