Colorectal CancerPhase 1NCT00873275
Ursodiol, Combination Chemotherapy, and Bevacizumab in Treating Patients With Stage IV Colorectal Cancer
A Phase 1 study testing bevacizumab, FOLFOX regimen and fluorouracil in people with Colorectal Cancer, run by City of Hope Medical Center at 1 site in United States.
Trial 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. 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?
- bevacizumab, FOLFOX regimen and fluorouracil
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Mar 2009to 26 Feb 2025
- Phase
- Phase 1
- 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
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010-3000
About this study
Official title: Phase I Study of Ursodeoxycholic Acid (Ursodiol)in Combination With 5-Fluorouracil, Leucovorin, Oxaliplatin and Bevacizumab in Patients With Metastatic Colorectal Cancer
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.
Read the detailed description
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.
- Conditions
- Colorectal Cancer
- Being tested
- bevacizumab, FOLFOX regimen, fluorouracil, leucovorin calcium, oxaliplatin
- Keywords
- stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
5mg/kg IV day 1 and 15 of each 28 day course of treatment
FOLFOX regimenDrug
Leucovorin, 5-FU and Oxaliplatin
fluorouracilDrug
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
400 mg/m2 IV infusion over 2 hours on days 1 and 15 of a 28 day course of treatment.
oxaliplatinDrug
85 mg/m2 IV infusion over 2 hours on days 1 and 15 of a 28 day course of treatment.
ursodiolDrug
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.
RNA analysisGenetic
Analysis on discard tissues
gene expression analysisGenetic
Determined in normal and malignant tissues in patients who undergo surgical resection after treatment on this trial
polymerase chain reactionGenetic
Analysis on discard tissues
western blottingGenetic
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
immunohistochemistry staining methodOther
Performed on tumor blocks from the primary and the metastases from the patients on study
laboratory biomarker analysisOther
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
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.
positron emission tomography (PET)Procedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum-tolerated dose of ursodiol
Measured: 28 days from the start of treatment
Toxicities as assessed by NCI CTCAE 3.0
Measured: 28 days after the last cycle of treatment
Survival
Measured: 2 years after treatment
Time to failure
Measured: 2 years after treatment
Pharmacokinetics of ursodiol
Measured: 8 days after start of treatment during course 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2009 (estimated)
- Study start11 Mar 2009
- Primary completion25 Sep 2012
- Study completion26 Feb 2025
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 City of Hope Medical 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Lily L. Lai, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00873275
- Sponsor's protocol ID
- 08005
- Other IDs
- P30CA033572, CHNMC-08005, CDR0000637521, NCI-2010-00926
- Status last verified
- Jun 2025
- First submitted
- 31 Mar 2009
- Last updated
- 22 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Ursodeoxycholic Acid (Ursodiol)in Combination With 5-Fluorouracil, Leucovorin, Oxaliplatin and Bevacizumab in Patients With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00873275
- Acronym / sponsor ID
- 08005
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 11 Mar 2009 (actual)
- Primary completion
- 25 Sep 2012 (actual)
- Study completion
- 26 Feb 2025 (actual)
- First posted
- 1 Apr 2009 (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: 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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ursodiol, combination chemotherapy, bevacizumab) | Experimental | 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)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (5 listed)
- 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
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 |
|---|---|---|
| bevacizumab5mg/kg IV day 1 and 15 of each 28 day course of treatment | Biological | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| FOLFOX regimenLeucovorin, 5-FU and Oxaliplatin | Drug | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| fluorouracil400 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 | Drug | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| leucovorin calcium400 mg/m2 IV infusion over 2 hours on days 1 and 15 of a 28 day course of treatment. | Drug | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| oxaliplatin85 mg/m2 IV infusion over 2 hours on days 1 and 15 of a 28 day course of treatment. | Drug | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| ursodiolDose 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. | Drug | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| RNA analysisAnalysis on discard tissues | Genetic | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| gene expression analysisDetermined in normal and malignant tissues in patients who undergo surgical resection after treatment on this trial | Genetic | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| polymerase chain reactionAnalysis on discard tissues | Genetic | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| western blottingDetermined 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 | Genetic | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| immunohistochemistry staining methodPerformed on tumor blocks from the primary and the metastases from the patients on study | Other | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| laboratory biomarker analysisPerformed 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 | Other | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| pharmacological studyDay 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. | Other | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
| positron emission tomography (PET)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. | Procedure or surgery | Treatment (ursodiol, combination chemotherapy, bevacizumab) |
Primary outcome
Maximum-tolerated dose of ursodiol
Time frame: 28 days from the start of treatment
Toxicities as assessed by NCI CTCAE 3.0
Time frame: 28 days after the last cycle of treatment
Survival
Time frame: 2 years after treatment
Time to failure
Time frame: 2 years after treatment
Pharmacokinetics of ursodiol
Time frame: 8 days after start of treatment during course 1
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 22 Jun 2025.
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
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.
Lily L. Lai, MD principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bevacizumab, FOLFOX regimen and fluorouracil in people with Colorectal Cancer, run by City of Hope Medical 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?
The sponsor lists 11 inclusion and 5 exclusion criteria. 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 22 Jun 2025. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Maximum-tolerated dose of ursodiol (time frame: 28 days from the start of treatment). The study lists 5 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 22 Jun 2025.