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

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

Interventions

BIOLOGICAL

bevacizumab

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

DRUG

FOLFOX regimen

Leucovorin, 5-FU and Oxaliplatin

DRUG

fluorouracil

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

DRUG

leucovorin calcium

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

DRUG

oxaliplatin

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

DRUG

ursodiol

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.

GENETIC

RNA analysis

Analysis on discard tissues

GENETIC

gene expression analysis

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

GENETIC

polymerase chain reaction

Analysis on discard tissues

GENETIC

western blotting

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

OTHER

immunohistochemistry staining method

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

OTHER

laboratory biomarker analysis

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

OTHER

pharmacological study

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.

PROCEDURE

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.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• City of Hope Medical Center

  lead OTHER

Principal Investigators

• Lily L. Lai, MD · City of Hope Medical Center

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-03-11

Primary Completion

2012-09-25

Completion

2025-02-26

Countries

• United States

Study Locations