Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Adenocarcinoma

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Gastrointestinal Agents

Bone Density Conservation Agents

Hematinics

Vitamins

Herbal and Botanical

Oxaliplatin

Bevacizumab

Leucovorin

Fluorouracil

Levoleucovorin

Calcium

Ursodeoxycholic Acid

Calcium, Dietary

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Hormones

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Cola

Folate

Vitamin B9

Patients receive oral ursodiol twice daily on days 1-28 (days -6 to 28 of course 1), leucovorin calcium IV over 2 hours on days 1 and 15, fluorouracil IV over 46 hours on days 1-2 and 15-16, and oxaliplatin IV over 2 hours and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

5mg/kg IV day 1 and 15 of each 28 day course of treatment

bevacizumab

FOLFOX regimen

400 mg/m2 IV bolus immediately following leucovorin on days 1 and 15 of a 28 day course of treatment. Then 2.4 gm/m2 IV continuous infusion over 46 hours immediately following bolus dose on days 1 and 2 and 15 and 16 of a 28 day course of treatment

fluorouracil

400 mg/m2 IV infusion over 2 hours on days 1 and 15 of a 28 day course of treatment.

leucovorin calcium

85 mg/m2 IV infusion over 2 hours on days 1 and 15 of a 28 day course of treatment.

oxaliplatin

Dose escalation in cohorts (3 patients/cohort) from an initial dose of 125 mg PO BID through 625 mgs PO BID beginning on Day -6 from infusion of bevacizumab and FOLFOX continuing for the duration of the treatment.

ursodiol

RNA analysis

Determined in normal and malignant tissues in patients who undergo surgical resection after treatment on this trial

gene expression analysis

polymerase chain reaction

Determined on blood collected at Day -6, Day 0 and Day 7 (1 week after the first cycle of chemotherapy) from treatment and at the end of treatment

western blotting

Performed on tumor blocks from the primary and the metastases from the patients on study

immunohistochemistry staining method

Performed on blood collected at Day -6, Day 0 and Day 7 (1 week after the first cycle of chemotherapy) from treatment and at the end of treatment

laboratory biomarker analysis

Day 0, day 7 before treatment, 1/2 hour after the start of treatment, 1, 2, 3, 4, and 8 hours after the start of treatment.

pharmacological study

Patients will undergo PET scan imaging as part of their original staging or at baseline. If the PET scan was more than 2 weeks prior to Day 0 from study treatment, there will be a PET scan at Day 0. In any case there will be a PET scan when the patient completes treatment.

positron emission tomography (PET)

Lily L. Lai, MD

RATIONALE: Drugs used in chemotherapy, such as ursodiol, oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Giving ursodiol together with leucovorin calcium, fluorouracil, oxaliplatin, and bevacizumab may be an effective treatment for colorectal cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of ursodiol when given together with combination chemotherapy and bevacizumab in treating patients with stage IV colorectal cancer.

OBJECTIVES:

Primary

* To determine the active dose and/or maximum tolerated dose of ursodiol when given in combination with fluorouracil, leucovorin calcium, oxaliplatin (FOLFOX regimen), and bevacizumab in patients with metastatic colorectal cancer.
* To determine the pharmacokinetics of ursodiol when given with this regimen.

Secondary

* To determine the systemic metabolic effects of ursodiol activation of nuclear receptor farnesoid X receptor (FXR) in glucose and lipid metabolism.
* To develop assays to detect ursodiol activation of FXR.
* To identify and evaluate potential serum biomarkers of FXR activation.
* To determine genes regulated by activation of FXR at target tissues.

OUTLINE: This is a dose-escalation study of ursodiol.

Patients receive oral ursodiol twice daily on days 1-28 (days -6 to 28 of course 1), leucovorin calcium intravenously (IV) over 2 hours on days 1 and 15, fluorouracil IV over 46 hours on days 1-2 and 15-16, and oxaliplatin IV over 2 hours and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Blood sample is collected periodically for pharmacokinetic studies. Samples are also analyzed for the role of nuclear receptor farnesoid X receptor (FXR) in glucose uptake and metabolism using PET scan imaging, an oral glucose tolerance test, and HbA1c levels; the effects of FXR activation on lipid metabolism; and a marker for response to FXR activation via western blot. Available formalin-fixed paraffin-embedded tumor tissue blocks are analyzed for FXR expressing via IHC; expression of known FXR target genes via RNA analysis and real-time PCR; and expression of genes involved in glucose metabolism.

Ursodiol, Combination Chemotherapy, and Bevacizumab in Treating Patients With Stage IV Colorectal Cancer

Phase I Study of Ursodeoxycholic Acid (Ursodiol)in Combination With 5-Fluorouracil, Leucovorin, Oxaliplatin and Bevacizumab in Patients With Metastatic Colorectal Cancer

National Cancer Institute (NCI)

City of Hope Medical Center

Rare Diseases

Carcinoma

Esophageal Neoplasms

Barrett Esophagus

Precancerous Conditions

Esophageal Diseases

Head and Neck Neoplasms

Esophageal Cancer

Patients receive ursodiol PO BID for 6 months in the absence of disease progression or unacceptable toxicity.

Ursodiol

Laboratory Biomarker Analysis

Bhaskar Banerjee

This pilot phase II trial studies how well ursodiol works in treating patients with Barrett esophagus or cells that look abnormal under a microscope but are not cancer (low-grade dysplasia). Chemoprevention is the use of certain drugs to keep cancer from forming. The use of ursodiol may keep cancer for forming in patients with Barrett esophagus or low-grade dysplasia.

PRIMARY OBJECTIVES:

I. To evaluate the ability of UDCA (ursodiol) treatment to reverse oxidative deoxyribonucleic acid (DNA) damage in the esophageal epithelium of subjects with Barrett's esophagus.

SECONDARY OBJECTIVES:

I. To determine the effects of UDCA treatment on gastric bile acid composition and on cell proliferation in Barrett's epithelium.

OUTLINE:

Patients receive ursodiol orally (PO) twice daily (BID) for 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 2 weeks.

Ursodiol in Treating Patients With Barrett Esophagus and Low-Grade Dysplasia

Clinical Study of Ursodeoxycholic Acid in Barrett's Patients

8OHdG will be assessed by percentage of positively stained nuclear area. A paired t-test at a one-sided 0.05 significance level will be used to assess change during intervention. The observed results will be reported along with the corresponding confidence intervals.

Results will be analyzed using paired t-tests. Results (mean values and changes during intervention) will be reported along with the corresponding confidence intervals.

Patients receive ursodiol PO BID for 6 months in the absence of disease progression or unacceptable toxicity.

Ursodiol: Given PO

Laboratory Biomarker Analysis: Correlative studies

Treatment (Ursodiol)

Patients receive ursodiol PO (13 to 15 mg/kg/day) BID for 6 months in the absence of disease progression or unacceptable toxicity.

Ursodiol: Given PO

Laboratory Biomarker Analysis: Correlative studies

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Sherry Chow

participants with fewer than 500 total nuclei in longitudinally sectioned crypts opening to the lumen were excluded from analysis

Reversal of Oxidative DNA Damage as Assessed by Changes in 8-hydroxy-2' -Deoxyguanosine (8OHdG) Immunostaining

analysis was limited to participants with baseline and 6-month gastric fluid

Changes in Gastric Bile Acid Composition (Change in Percent of Total Bile Acid Present as Ursodeoxycholic Acid and Its Glycine/Taurine Conjugates) Measured by Liquid Chromatography-tandem Mass Spectrometry, From Baseline to Post-intervention

Changes in Gastric Bile Acid Composition (Change in Percent of Total Bile Acid Present as Deoxycholic Acid and Its Glycine/Taurine Conjugates) Measured by Liquid Chromatography-tandem Mass Spectrometry, From Baseline to Post-intervention

tissue slides with fewer than 500 total nuclei in longitudinally sectioned crypts opening to the lumen were excluded from analysis

Changes in Cell Proliferation in BE Epithelium From Baseline to Post-intervention as Assessed by Proliferation-related Ki-67 Antigen (Ki67) Immunostaining, Percentage of Positively Stained Nuclei, in BE Tissue Sections

Overall Study

Antipyretics

Anti-Inflammatory Agents

Antirheumatic Agents

Fibrinolytic Agents

Analgesics

Platelet Aggregation Inhibitors

Aspirin

Sulindac

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Patients receive oral aspirin once daily for 12 months.

Acetylsalicylic acid (Aspirin)

Patients receive oral sulindac twice daily for 12 months.

Patients receive oral ursodiol three times daily for 12 months.

Sulindac Placebo

Robert S. Bresalier, MD

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. It is not yet known whether sulindac, aspirin, or ursodiol is more effective in preventing colorectal cancer.

PURPOSE: This randomized phase II trial is studying how well sulindac works compared to aspirin or ursodiol in preventing colorectal cancer.

OBJECTIVES:

* Determine the percentage change in colorectal aberrant crypt foci (ACF) in patients with a history of colorectal cancer or at high risk for colorectal cancer when treated with sulindac vs aspirin vs ursodiol.
* Determine the safety and efficacy of these drugs, in terms of ability to cause regression of existing colorectal ACF and prevent new ACF development, in these patients.

OUTLINE: This is a partially blinded, randomized, placebo-controlled study. Patients are stratified according to colorectal neoplasia (adenoma vs carcinoma). Patients are randomized to 1 of 4 treatment arms.

* Arm I: Patients receive oral sulindac twice daily.
* Arm II: Patients receive oral aspirin once daily.
* Arm III: Patients receive oral ursodiol three times daily.
* Arm IV: Patients receive oral sulindac placebo twice daily. In all arms, treatment continues for 12 months in the absence of disease progression or unacceptable toxicity.

Patients undergo a colonoscopy at baseline and at the end of treatment.

Patients are followed at 2 months after the end of treatment.

PROJECTED ACCRUAL: A total of 172 patients (43 per treatment arm) with a history of colorectal cancer or adenomas will be accrued for this study. A total of 20 additional patients with no elevated risk of colorectal neoplasia will be accrued, but not randomized, for this study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ursodiol, Combination Chemotherapy, and Bevacizumab in Treating Patients With Stage IV Colorectal Cancer	NCT00873275	Colorectal Canc...	bevacizumab FOLFOX regimen fluorouracil leucovorin calc... oxaliplatin ursodiol RNA analysis gene expression... polymerase chai... western blottin... immunohistochem... laboratory biom... pharmacological... positron emissi...	18 Years -	City of Hope Medical Center
Ursodiol in Treating Patients With Barrett Esophagus and Low-Grade Dysplasia	NCT01097304	Barrett Esophag... Esophageal Carc...	Ursodiol Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Ursodiol in Treating Patients With Barrett Esophagus and Low-Grade Dysplasia	NCT01097304	Barrett Esophag... Esophageal Carc...	Ursodiol Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Comparison of Sulindac, Aspirin, and Ursodiol in Preventing Colorectal Cancer	NCT00062023	Colorectal Canc...	Acetylsalicylic... Sulindac Ursodiol Sulindac Placeb...	40 Years - 80 Years	M.D. Anderson Cancer Center
Ursodiol in Treating Patients With Barrett Esophagus and Low-Grade Dysplasia	NCT01097304	Barrett Esophag... Esophageal Carc...	Ursodiol Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Ursodiol in Treating Patients With Barrett Esophagus and Low-Grade Dysplasia	NCT01097304	Barrett Esophag... Esophageal Carc...	Ursodiol Laboratory Biom...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for ursodiol

Every month we try and update this database with for ursodiol cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ursodiol

Every month we try and update this database with for ursodiol cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ursodiol cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.