Colorectal CancerNCT00280761
Biomarkers in Patients With Rectal Cancer Undergoing Chemotherapy and Radiation Therapy
An observational study of Colorectal Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- capecitabine, 5-fluorouracil and Surgical Resection
- Type of treatment
- Surgery or procedure
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2003to 19 Sep 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
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
Trial locations and contacts
1 site in 1 country.
United States1 site
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295
About this study
Official title: A Biologic Study of Global Gene Expression, NF-Kappa B and p53 in Adenocarcinoma of the Rectum.
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.
Read the 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
- Being tested
- capecitabine, 5-fluorouracil, Surgical Resection, Radiation therapy
- Keywords
- adenocarcinoma of the rectum, recurrent rectal cancer, stage II rectal cancer, stage III rectal cancer, stage IV rectal cancer
- Medical subject headings
- Colorectal Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
capecitabineDrug
Also called Xeloda
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-fluorouracilDrug
Also called 5-FU
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 ResectionProcedure or surgery
Surgery will occur approximately 2-6 weeks after chemoradiation depending on clinical factors (i.e. resectability, presence or absence of metastatic disease).
Radiation therapyRadiation
Also called EBRT - External Beam Radiation Therapy
Dosing and dose modification will be per current standard of care at the discretion of the treating Radiation Oncologist.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Single Arm Trial Receives: Drug: capecitabine; Drug: 5-fluorouracil; Procedure: Surgical Resection; Radiation: Radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Activation of NF-kappa B in response to treatment with external beam radiotherapy
Measured: 6-8 weeks after chemoradiation
Correlation of NF-kappa B pathway activation with therapeutic outcomes
Measured: 6-8 weeks after chemoradiation
Secondary outcomes (5)
Downstream events induced by NF-kappa B activation
Measured: 12 months
Global gene expression profiles at baseline and during chemoradiotherapy
Measured: prior to chemoradiation and 72 days post chemoradiation
Correlation of changes in gene expression with patient outcomes
Measured: 72 days post chemoradiation
Downstream events related to activation of p53 in response to treatment with radiotherapy
Measured: 72 post radiotherapy
Correlation of p53 pathway-mediated events with clinical outcomes
Measured: 72 days post chemoradiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2006 (estimated)
- Study startDec 2003
- Primary completion19 Sep 2021
- Study completion19 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Hanna Sanoff, MD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00280761
- Sponsor's protocol ID
- LCCC 0216
- Other IDs
- P30CA016086, CDR0000561688
- Status last verified
- Aug 2022
- First submitted
- 19 Jan 2006
- Last updated
- 11 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Biologic Study of Global Gene Expression, NF-Kappa B and p53 in Adenocarcinoma of the Rectum.
- ClinicalTrials.gov ID
- NCT00280761
- Acronym / sponsor ID
- LCCC 0216
- Conditions
- Colorectal Cancer
- Keywords
- adenocarcinoma of the rectum, recurrent rectal cancer, stage II rectal cancer, stage III rectal cancer, stage IV rectal cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2003
- Primary completion
- 19 Sep 2021 (actual)
- Study completion
- 19 Sep 2021 (actual)
- First posted
- 23 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Drug: capecitabine, Drug: 5-fluorouracil, Procedure: Surgical Resection, Radiation: Radiation therapySingle Arm Trial |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| capecitabineAlso: XelodaCapecitabine 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 | Drug | 1 |
| 5-fluorouracilAlso: 5-FUAdministration 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. | Drug | 1 |
| Surgical ResectionSurgery will occur approximately 2-6 weeks after chemoradiation depending on clinical factors (i.e. resectability, presence or absence of metastatic disease). | Procedure or surgery | 1 |
| Radiation therapyAlso: EBRT - External Beam Radiation TherapyDosing and dose modification will be per current standard of care at the discretion of the treating Radiation Oncologist. | Radiation | 1 |
Primary outcome
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
5 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2022.
- web address for UNC Lineberger Comprehensive Cancer CenterLink provided by the sponsor.
- web address for the National Cancer Institute (NCI)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hanna Sanoff, MD principal investigator
UNC Lineberger Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colorectal Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Activation of NF-kappa B in response to treatment with external beam radiotherapy (time frame: 6-8 weeks after chemoradiation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2022.