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

NCT00873275 | Completed Phase 1 DMC

• 5 other identifiers: 08005P30CA033572CHNMC-08005CDR0000637521NCI-2010-00926
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

stage IV colon cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (5)

• Maximum-tolerated dose of ursodiol

  28 days from the start of treatment

• Toxicities as assessed by NCI CTCAE 3.0

  28 days after the last cycle of treatment

• Survival

  2 years after treatment

• Time to failure

  2 years after treatment

• Pharmacokinetics of ursodiol

  8 days after start of treatment during course 1

Study Arms (1)

Treatment (ursodiol, combination chemotherapy, bevacizumab)

EXPERIMENTAL

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.

Biological: bevacizumab; Drug: FOLFOX regimen; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Drug: ursodiol; Genetic: RNA analysis; Genetic: gene expression analysis; Genetic: polymerase chain reaction; Genetic: western blotting; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: positron emission tomography (PET)

Interventions

bevacizumab BIOLOGICAL

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

Treatment (ursodiol, combination chemotherapy, bevacizumab)

FOLFOX regimen DRUG

Leucovorin, 5-FU and Oxaliplatin

Treatment (ursodiol, combination chemotherapy, bevacizumab)

fluorouracil DRUG

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

Treatment (ursodiol, combination chemotherapy, bevacizumab)

leucovorin calcium DRUG

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

Treatment (ursodiol, combination chemotherapy, bevacizumab)

oxaliplatin DRUG

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

Treatment (ursodiol, combination chemotherapy, bevacizumab)

ursodiol DRUG

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.

Treatment (ursodiol, combination chemotherapy, bevacizumab)

RNA analysis GENETIC

Analysis on discard tissues

Treatment (ursodiol, combination chemotherapy, bevacizumab)

gene expression analysis GENETIC

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

Treatment (ursodiol, combination chemotherapy, bevacizumab)

polymerase chain reaction GENETIC

Analysis on discard tissues

Treatment (ursodiol, combination chemotherapy, bevacizumab)

western blotting GENETIC

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

Treatment (ursodiol, combination chemotherapy, bevacizumab)

immunohistochemistry staining method OTHER

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

Treatment (ursodiol, combination chemotherapy, bevacizumab)

laboratory biomarker analysis OTHER

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

Treatment (ursodiol, combination chemotherapy, bevacizumab)

pharmacological study OTHER

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.

Treatment (ursodiol, combination chemotherapy, bevacizumab)

positron emission tomography (PET) PROCEDURE

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.

Treatment (ursodiol, combination chemotherapy, bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced, biopsy proven metastatic colorectal cancer
• Karnofsky Performance Status \>= 80
• Prior therapy completed at least 3 weeks before protocol treatment initiation with recovery from any side-effects
• Serum albumin and prealbumin within normal limits
• Alanine aminotransferase (ALT) within 3 x upper limit of normal
• Alkaline phosphatase within 3 x upper limit of normal
• Serum bilirubin within normal limits
• Absolute neutrophil count \>= 1500/ul
• Serum creatinine within 1.5 x upper limit of normal
• Ability to understand and sign an institutional review board (IRB) approved informed consent
• Ability to use appropriate contraception and no evidence of pregnancy in female patients of reproductive potential

You may not qualify if:

• Significant medical or psychiatric condition that would make treatment unsafe
• Use of systemic steroids use within 7 days from start of trial
• Nursing women
• Patients unable to comply with protocol related studies and follow up
• Weight loss of greater than 10% in the last 6 months

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010-3000, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Folfox protocol; Fluorouracil; Leucovorin; Oxaliplatin; Ursodeoxycholic Acid; Gene Expression Profiling; Polymerase Chain Reaction; Blotting, Western; Immunohistochemistry; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Genetic Techniques; Investigative Techniques; Nucleic Acid Amplification Techniques; Electrophoresis; Chemistry Techniques, Analytical; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Spectrum Analysis

Study Officials

• Lily L. Lai, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2009
• First Posted: April 1, 2009
• Study Start: March 11, 2009
• Primary Completion: September 25, 2012
• Study Completion: February 26, 2025
• Last Updated: June 22, 2025

Record last verified: 2025-06

Locations

US (1)