Neoplasms

Digestive System Diseases

All Conditions

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stephanie N Hicks

Tim F Greten, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

- Gastrointestinal cancers can occur in the throat, stomach, gallbladder, liver, pancreas, and colon. Researchers are interested in evaluating how active the immune system is in trying to fight the cancer by studying blood and tumor tissue donated from individuals who have been diagnosed with gastrointestinal cancers.

Objectives:

- To collect blood and tumor samples from individuals who have been diagnosed with gastrointestinal cancers in order to study the immune system s response to the cancer.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with throat, stomach, gallbladder, liver, pancreatic, or colon cancer, and are scheduled to be treated at the National Institutes of Health.

Design:

* The study will require at least one but no more than four visits to the National Institutes of Health Clinical Center.
* Participants will be screened with a physical examination and medical history, and will provide a baseline blood sample for study.
* Participants will provide additional blood samples 2 and 4 months after the baseline sample, as well as a final sample at the completion of the treatment protocol.
* Participants will provide tumor tissue samples only if they undergo a surgical procedure related to the treatment for their gastrointestinal cancer.
* No treatment will be provided as part of this protocol.

BACKGROUND:

* Numerous recent therapeutic advances have changed standard treatment options for patients with GI cancer. These include newer chemotherapeutic agents in addition to established proof of principle for anti-angiogenic agents. The burden of GI cancers is reflected by the presence of three GI cancer types in the top five causes of cancer mortality. Over 58,000 deaths yearly can be attributed to GI cancer.
* While immune-based therapies in GI cancers are experimental at the current time, a gathering body of literature is suggestive of an enormous potential, either alone, or most likely in combination with standard chemotherapy.
* Before immunotherapy can be combined with non-immune based treatment options we first need to investigate the effects of non-immune based therapies on immune responses (especially immune-evasive mechanisms) with cancer.
* Commensal gut microbiota play an important role in colonic inflammation and colon cancer. The human gut flora consists of approximately 100 trillion microbial cells, which their disruption leads to many types of diseases including inflammatory bowel disease and colorectal cancer. Recent studies have shown that colon cancer patients as well other patients with gastrointestinal cancers have an altered gut flora when compared to healthy controls. As an example, intestinal microbiome has been shown to contribute to the start and progression of certain kinds of liver diseases such as NAFLD as well as end-stage liver diseases 2-4 Therefore, it is important to investigate further as to how the gut affects the patient s response to chemotherapy, other types of cancer therapy and to tumor growth in general.

OBJECTIVES:

To serve as an umbrella protocol to allow collection, storage and investigation of samples from patients with gastrointestinal (GI) cancers in support of Thoracic and GI Oncology Branch translational trials to develop new therapeutic agents and novel treatment approaches as well as new prognostic and diagnostic models. Also, to collect samples from patients with non-GI cancers for comparison.

ELIGIBILITY:

* Patients undergoing evaluation for participation in NCI treatment protocols in the NCI intramural program with diagnosis of cancer.
* 18 year of age or older.

DESIGN:

* Blood, tumor tissue or stool samples may be collected from consenting subjects at the initial visit and/or at the time of visit to NIH, scheduled per other NIH protocols.
* Analysis of subject s samples include but not limited to immune-monitoring, single cell sequencing, identifying of gene expression and generation of CAR-T cells.
* Stool samples will be used to determine the intestinal microbiome.

Acquisition of Blood and Tumor Tissue Samples From Patients With Gastrointestinal Cancer

.All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP

Collected blood, tumor samples from patients with gastrointestinal (GI) cancers being reviewed by Medical Oncology Branch and to perform immune studies

National Cancer Institute (NCI)

Nervous System Diseases

Peripheral Nervous System Diseases

Neuromuscular Diseases

Antineoplastic Agents

All Drugs and Chemicals

Oxaliplatin

polymorphism analysis

Inas M Moukhtar Ahmed, B.pharma

Lamia M El Wakeel, Assoc. Prof

Abdel Hady A Abdel Wahab, Professor

Amr S Saad, Assoc. Prof

Raafat R Abdel-Malek, Assoc. Prof

This study will examine DNA from Gastrointestinal Tract of cancer patients treated with oxaliplatin to look for a variation (mutation) of the ABCG2 gene that may lead to drug-induced peripheral neuropathy in certain patients.

The DNA will be extracted from patients' blood samples and are analyzed for the ABCG2 single nucleotide polymorphism (G34A - rs2231137 and A/A -rs3114018 genotypes) and correlated with peripheral neuropathy grades.

Pharmacogenetic analysis/genotyping :

Genotyping is conducted via High Resolution Melting (HRM) TECHNIQUE, To confirm the genotyping results, the Polymerase chain reaction (PCR) product of the samples will be examine via direct sequencing using 3500 Genetic analyzer from ThermoFisher (applied biosystem) at two ABCG2 loci using the following PCR primers:

1-ABCG2 G34A - rs2231137

Forward :

5'-TGC AAT CTC ATT TAT CTG GAC TA-'3

Reverse :

5'-AAT GCC TTC AGG TCA TTG GA-'3

-Annealing temp :57 -Product size : 163

2- ABCG2 A/A - rs3114018

Forward :

5'- TGATGTTCCTTCAGCCACTG-'3

Reverse :

5'-TTGTGGAAACCTCACAAAAGTG-'3

- Annealing temp : 59 - Product size : 124

Oxaliplatin - Induced Peripheral Neuropathy in Patients With Gastrointestinal Tract Cancer

Relation of Genetic Polymorphism of ABCG2 Gene And Occurrence of Oxaliplatin - Induced Peripheral Neuropathy in Patients With Gastrointestinal Tract Cancer

Peripheral Neuropathy Toxicity will be assessed every cycle for six months using the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE). Patients will be assigned to 4 groups according to the grades of neuropathy.

Ain Shams University

African Union,organization St. Abbsia, Cairo, Egypt

Background:

- Gastrointestinal cancers can occur in the throat, stomach, gallbladder, liver, pancreas, and colon. Researchers are interested in evaluating how active the immune system is in trying to fight the cancer by studying blood and tumor tissue donated from individuals who have been diagnosed with gastrointestinal cancers.

Objectives:

- To collect blood and tumor samples from individuals who have been diagnosed with gastrointestinal cancers in order to study the immune system s response to the cancer.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with throat, stomach, gallbladder, liver, pancreatic, or colon cancer, and are scheduled to be treated at the National Institutes of Health.

Design:

* The study will require at least one but no more than four visits to the National Institutes of Health Clinical Center.
* Participants will be screened with a physical examination and medical history, and will provide a baseline blood sample for study.
* Participants will provide additional blood samples 2 and 4 months after the baseline sample, as well as a final sample at the completion of the treatment protocol.
* Participants will provide tumor tissue samples only if they undergo a surgical procedure related to the treatment for their gastrointestinal cancer.
* No treatment will be provided as part of this protocol....

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Esophageal Neoplasms

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Stomach Diseases

Head and Neck Neoplasms

Esophageal Diseases

Rectal Diseases

Esophageal Cancer

Stomach Cancer

Small Intestine Cancer

Tegafur

Capecitabine

Antimetabolites

Oxaliplatin 130 mg/m2 d. 1 followed by oral S-1 25 mg/m2/day BID d1-14.

Intravenous oxaliplatin 130 mg/m2 d.1 followed by oral capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14.

S-1 25 mg/m2/day BID d1-14, oxaliplatin injection 130 mg/m2 D1 every 3 weeks

capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14, oxaliplatin injection 130 mg/m2 D1 every 3 weeks

Heikki Joensuu, MD

Fluoropyrimidine chemotherapy agents , such as 5-fluorouracil and capecitabine, are occasionally associated with cardiac toxicity. Clinical fluoropyrimidine cardiotoxicity is infrequent, but subclinical toxicity may be much more common. Cardiac toxicity may be less frequent with S-1 as compared with 5-fluorouracil and capecitabine, but head-to-head comparisons are lacking. The purpose of the study is to compare 2 measures of subclinical coronary artery microvascular dysfunction, the coronary flow reserve and the coronary flow response to a cold pressor test, in a patient population who are being treated for adenocarcinoma of the gastrointestinal tract with one of 2 oxaliplatin-containing regimens, either with oxaliplatin plus S-1 or with oxaliplatin plus capecitabine.

Patients diagnosed with adenocarcinoma of the gastroesophageal tract are randomly assigned to receive two 3-weekly cycles of either XELOX (intravenous oxaliplatin 130 mg/m2 d.1 followed by oral capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14) or SOX (intravenous oxaliplatin 130 mg/m2 d. 1 followed by oral S-1 25 mg/m2/day BID d1-14). A cross-over between the 2 arms is carried out after the first 2 cycles; patients allocated to XELOX will receive 2 cycles of SOX (cycles 3 and 4), and those allocated to SOX will receive XELOX (cycles 3 and 4). Monitoring of the coronary artery flow, cardiac arrythmias, cardiac symptoms and blood biochemistry is done at baseline, during each chemotherapy cycle (cycles 1 to 4) and after treatment.Study treatment will continue until all patients have discontinued from treatment or maximum 24 weeks from the date of the first day of treatment, whichever occurs first. At that point, treatment may continue at the discretion of the Investigator. Each patient will be followed for survival status for a minimum of 12 months after first dose of study medication. Tumor assessments will be performed throughout the study period and analyzed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009). Computed tomography (CT) scans will be performed at the end of every 2 cycles. Cardiac assessments will be performed and analyzed using non-invasive transthoracic Doppler echocardiography, 24-h Holter registration, and plasma troponin concentration.

Effects of S-1 and Capecitabine on Coronary Artery Blood Flow

Effects of S-1 and Capecitabine in Combination With Oxaliplatin on the Coronary Artery Blood Flow in Patients Metastatic Gastrointestinal Tract Adenocarcinoma: a Randomized Phase II Study

The frequency of subclinical coronary artery dysfunction is as assessed by comparing the coronary flow reserve during chemotherapy with the baseline coronary flow reserve, and the coronary flow response to a cold pressor test.

The coronary artery blood flow rate is measured with ultrasound. The rates are compared with the baseline and between the groups.

Cardiac arrythmias detected with Holter cardiac recording.

Survival from the first dose of study medication to study completion

Heikki Joensuu

MD, professor

Carotenoids

Antioxidants

Protective Agents

In each study, the serum concentrations of carotenoids were detected by high performance liquid chromatography

serum carotenoids

Previous studies have suggested that serum carotenoids may be associated with risk of gastrointestinal tract cancer (GIT cancer), but the results were inconsistent. Thus, the investigators conducted a meta-analysis to evaluate the associations between serum carotenoids and risk of GIT cancer.

Serum Carotenoids and Risk of Gastrointestinal Tract Cancer: Meta-analysis of Ten Studies

The gastrointestinal tract cancer incident would be recorded during the follow-up years.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Acquisition of Blood and Tumor Tissue Samples From Patients With Gastrointestinal Cancer	NCT01313442	Non-GI Cancers Cancer of Gastr... Gastrointestina...		18 Years -	National Institutes of Health Clinical Center (CC)
Oxaliplatin - Induced Peripheral Neuropathy in Patients With Gastrointestinal Tract Cancer	NCT02428101	Gastrointestina... Peripheral Neur...	polymorphism an...	18 Years - 80 Years	Ain Shams University
Oxaliplatin - Induced Peripheral Neuropathy in Patients With Gastrointestinal Tract Cancer	NCT02428101	Gastrointestina... Peripheral Neur...	polymorphism an...	18 Years - 80 Years	Ain Shams University
Acquisition of Blood and Tumor Tissue Samples From Patients With Gastrointestinal Cancer	NCT01313442	Non-GI Cancers Cancer of Gastr... Gastrointestina...		18 Years -	National Institutes of Health Clinical Center (CC)
Effects of S-1 and Capecitabine on Coronary Artery Blood Flow	NCT02216149	Esophagus Cance... Stomach Cancer Small Bowel Can... Colon Cancer Rectum Cancer	S-1 Capecitabine Oxaliplatin	18 Years - 100 Years	Helsinki University Central Hospital
Oxaliplatin - Induced Peripheral Neuropathy in Patients With Gastrointestinal Tract Cancer	NCT02428101	Gastrointestina... Peripheral Neur...	polymorphism an...	18 Years - 80 Years	Ain Shams University
Effects of S-1 and Capecitabine on Coronary Artery Blood Flow	NCT02216149	Esophagus Cance... Stomach Cancer Small Bowel Can... Colon Cancer Rectum Cancer	S-1 Capecitabine Oxaliplatin	18 Years - 100 Years	Helsinki University Central Hospital
Serum Carotenoids and Risk of Gastrointestinal Tract Cancer: Meta-analysis of Ten Studies	NCT03433092	Gastrointestina...	serum carotenoi...	-	West China Hospital

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