Biomarkers in Patients With Rectal Cancer Undergoing Chemotherapy and Radiation Therapy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00280761|
Recruitment Status : Recruiting
First Posted : January 23, 2006
Last Update Posted : March 21, 2017
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 or disease||Intervention/treatment|
|Colorectal Cancer||Drug: capecitabine Drug: 5-fluorouracil Procedure: Surgical Resection Radiation: Radiation therapy|
- 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]).
- 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.
|Study Type :||Observational|
|Estimated Enrollment :||60 participants|
|Official Title:||A Biologic Study of Global Gene Expression, NF-Kappa B and p53 in Adenocarcinoma of the Rectum.|
|Study Start Date :||December 2003|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2021|
Single Arm Trial
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: XelodaDrug: 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-FUProcedure: 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
- Activation of NF-kappa B in response to treatment with external beam radiotherapy [ Time Frame: 6-8 weeks after chemoradiation ]
- Correlation of NF-kappa B pathway activation with therapeutic outcomes [ Time Frame: 6-8 weeks after chemoradiation ]
- Downstream events induced by NF-kappa B activation [ Time Frame: 12 months ]
- Global gene expression profiles at baseline and during chemoradiotherapy [ Time Frame: prior to chemoradiation and 72 days post chemoradiation ]
- Correlation of changes in gene expression with patient outcomes [ Time Frame: 72 days post chemoradiation ]
- Downstream events related to activation of p53 in response to treatment with radiotherapy [ Time Frame: 72 post radiotherapy ]
- Correlation of p53 pathway-mediated events with clinical outcomes [ Time Frame: 72 days post chemoradiation ]
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00280761
|Contact: Amber Kriger, BSfirstname.lastname@example.org|
|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|
|Principal Investigator:||Cheryl Carlson, MD||UNC Lineberger Comprehensive Cancer Center|