Clinical trial NCT01445327: Predictors of Tumor Response and of Radiation Therapy Side Effects in Patients With Gastrointestinal Cancers
Official title: A Pilot Study of Markers of Tumor Burden and Radiation Toxicity in the Blood, Urine, and Stool of Patients Receiving Radiotherapy for Gastrointestinal Malignancies
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Esophageal Cancer
Stomach Cancer
Pancreatic Cancer
Keywords: Blood
Urine
Stool
Tumor Marker
Radiation Therapy
Gastrointestinal Cancer
Esophageal Cancer
Stomach
Pancreatic Cancer
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2011-10-03
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with gastrointestinal tumors that will receive radiation therapy at the National Institutes of Health (NIH) Clinical Center as part of their treatment.

Brief summary: Background:

* Gastrointestinal cancers are among the most commonly diagnosed cancers in the United States.
* There are currently no tests to predict how patients with gastrointestinal cancers will respond to radiation therapy or which patients may develop side effects from treatment.
* Studies on tumor cells in the stool, urine, or blood from patients may provide valuable information that can be used to develop tests to determine which patients may need more or less aggressive therapy.
* Studies of other substances in the stool, urine, or blood from patients may provide valuable information that can be used to develop tests to determine which patients are likely to develop side effects from radiation treatments.

Objectives:

* To collect blood, urine and stool specimens from patients with gastrointestinal cancers who will undergo radiation therapy.
* To study hormone and protein changes in these blood, urine and stool specimens before, during and after radiation treatment in order to develop a way to predict how gastrointestinal cancers will respond to radiation therapy and if patients with these cancers will develop side effects from radiation treatment.

Eligibility:

-Patients 18 years of age and older with cancer of the gastrointestinal tract (esophagus, stomach, pancreas, rectum) who plan to receive radiotherapy to the site of the cancer on an National Cancer Institute (NCI) protocol

Design:

Participants undergo the following procedures:

* Tumor biopsy: Before any treatment or at the time of surgery if it is the first treatment
* Urine collection: Before, during, and after treatment and at follow-up visits.
* Stool collection: Before, during, and after treatment and at follow-up visits.
* Blood collection: Before, during, and after treatment and at follow-up visits.
* Intestinal permeability assessment: Before any treatment, before radiation (if radiation is not the first treatment), 1 month after radiation is completed, and 3 months after radiation is completed. This test determines how the patients intestines are working to absorb sugar and may provide information about side effects from radiation treatments. Patients fast after midnight, then drink a small glass of sugars, and then do a 6-hour urine collection.

Detailed description: Background:

* Gastrointestinal (GI) carcinomas represent one of the most commonly diagnosed malignancies in the United States.
* A sensitive and specific marker of tumor persistence or recurrence would permit a more accurate determination of the appropriateness of adjuvant therapy in patients with no clinical evidence of disease following curative resection and allow the diagnosis of recurrences at earlier stages that may be amenable to curative salvage therapies.
* A biomarker detectable shortly after treatment or in the early stages of chronic radiation toxicity may allow the identification of patients at risk and early intervention.

Objectives:

* Our primary objective is to determine if patient specific tumor markers in stool, urine, or serum can be reliably detected prior to treatment and followed after treatment to monitor the extent of residual disease.
* A second objective is to evaluate the predictive value of potential markers of chronic gastrointestinal injury after radiotherapy.

Eligibility:

* Age greater than or equal to 18 years
* Histologically confirmed carcinoma of the gastrointestinal tract (esophagus, stomach, pancreas, rectum)
* Planned to receive radiotherapy to the site of the gastrointestinal malignancy on an National Cancer Institute (NCI) protocol

Design:

* This protocol provides a means of acquiring tissue, serum, urine, and stool samples from patients who will receive radiation therapy as part of their treatment for gastrointestinal malignancies.
* Patients treated with radiation therapy on NCI treatment protocols will be asked to provide samples prior to any local or systemic therapy as well as before, during and after their radiation treatment.
* These samples will be tested for the presence of tumor specific deoxyribonucleic acid (DNA) mutations and aberrant methylation patterns determined to be present in each patient's tumor by screening of initial biopsy or surgical material.
* Tumor markers specific to each patient, such as tumor specific DNA mutations or aberrant DNA methylation, may provide an individualized method to evaluate disease status and determine prognosis after therapy. Additionally, a number of stool and serum markers will be explored as early indicators of acute and eventual chronic gastrointestinal injury in patients receiving radiotherapy to the abdomen.

Eligibility criteria: * INCLUSION CRITERIA:
* Age greater than or equal to 18 years.
* Histologically confirmed carcinoma of the gastrointestinal tract (esophagus, stomach, pancreas, bile duct, rectum).
* Treatment plan includes radiotherapy to the site of the gastrointestinal malignancy on an National Cancer Institute (NCI) protocol.
* Paraffin embedded tumor tissue from biopsy or surgery adequate in amount to perform polymerase chain reaction (PCR) and methylation specific PCR or willingness to undergo re-biopsy.

EXCLUSION CRITERIA:

* Inability to provide informed consent.
* Patients who have a history of prior therapeutic radiation.
* Patients with evidence of distant metastases on initial staging evaluation.
* Patients with other cancers excluding non-melanomatous skin cancers or carcinoma in situ.
* History of inflammatory bowel disease.
* History of collagen vascular disease or disease of altered collagen metabolism (end stage renal disease or hepatic fibrosis due to chronic hepatitis).
* History of hypersensitivity to radiation or a history of a disease which results in mucosal or other hypersensitivity to radiation (Ataxia-Telangiectasia, Bloom's Syndrome, Human Immunodeficiency Virus, Fanconi anemia, nevoid basal cell carcinoma syndrome, Li-Fraumeni syndrome, and Nijmegen breakage syndrome).
* Inability to return for follow-up visits.
* Patients who have previously received or are currently receiving MDX-101 (ipilimumab).
* Diagnosis of human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C.

Primary outcomes:
measure: Number of Participants With Specific Tumor Markers in Stool, Urine, or Serum Detected Prior to Treatment and After Treatment
timeFrame: Prior to treatment (baseline) and after treatment, up to 19 months
Secondary outcomes:
measure: Number of Participants With Chronic Gastrointestinal Injury After Radiotherapy
timeFrame: After radiotherapy, up to 19 months
Other outcomes:
measure: Here is the Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC) v3.0.
timeFrame: Date treatment consent signed to date off study, an average of 19 months
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Deborah E Citrin, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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