Hepatic Arterial Infusion of Floxuridine, Gemcitabine Hydrochloride, and Radiolabeled Monoclonal Antibody Therapy in Treating Liver Metastases in Patients With Metastatic Colorectal Cancer Previously Treated With Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00645710
First received: March 27, 2008
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as floxuridine and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hepatic arterial infusion uses a catheter to carry cancer-killing substances directly into the liver. Radiolabeled monoclonal antibodies can find tumor cells and carry tumor-killing substances to them without harming normal cells. Giving hepatic arterial infusion of floxuridine together with gemcitabine hydrochloride and radiolabeled monoclonal antibody therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase I/II trial is studying the side effects and best dose of floxuridine when given as a hepatic arterial infusion together with gemcitabine hydrochloride and radiolabeled monoclonal antibody therapy and to see how well it works in treating liver metastases in patients with metastatic colorectal cancer.


Condition Intervention Phase
Liver Metastases
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Drug: gemcitabine hydrochloride
Drug: floxuridine
Genetic: proteomic profiling
Other: matrix-assisted laser desorption/ionization time of flight mass spectrometry
Other: liquid chromatography
Radiation: yttrium Y 90 anti-CEA monoclonal antibody cT84.66
Other: laboratory biomarker analysis
Other: mass spectrometry
Other: pharmacological study
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Radioimmunotherapy (Y-90 cT84.66), Gemcitabine and Hepatic Arterial Infusion of Fudr for Metastatic Colorectal Carcinoma to the Liver

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
  • Sites of recurrence [ Time Frame: At 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 28
Study Start Date: February 2005
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV over 25 minutes on day 9. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients may receive an additional course of floxuridine in combination with systemic therapy at the discretion of the treating physician.

Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • dFdCyd
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
  • LY-188011
Drug: floxuridine
Given via hepatic arterial infusion
Other Names:
  • 5-FUDR
  • FdUrD
  • floxuridin
  • fluorodeoxyuridine
  • fluoruridine deoxyribose
  • FUdR
Genetic: proteomic profiling
Correlative studies
Other: matrix-assisted laser desorption/ionization time of flight mass spectrometry
Correlative studies
Other Name: MALDI-TOF Mass Spectrometry
Other: liquid chromatography
Correlative studies
Other Name: LC
Radiation: yttrium Y 90 anti-CEA monoclonal antibody cT84.66
Given IV
Other: laboratory biomarker analysis
Correlative studies
Other: mass spectrometry
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and associated toxicities of concurrent hepatic arterial infusion (HAI) fluorodeoxypyrimidine (FUdR)/Decadron and intravenous gemcitabine combined with intravenous yttrium-90 (^90Y) chimeric T84.66 (cT84.66) in colorectal cancer patients after hepatic resection or maximum surgical debulking (to < 3 cm) of liver metastases.

II. To study the feasibility and toxicities of such adjuvant therapy following resection and/or ablation of liver metastases.

III. To evaluate the biodistribution, clearance and metabolism of ^90Y and ^111In (indium-iii) chimeric T84.66 administered intravenously.

IV. To estimate radiation doses to whole body, normal organs, and tumor through serial nuclear imaging.

V. To correlate proteomic profiles pre and post-therapy with toxicities and anti-tumor effects.

OUTLINE: This is a phase I, dose-escalation study of floxuridine followed by a phase II study.

Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV over 25 minutes on day 9. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients may receive an additional course of floxuridine in combination with systemic therapy at the discretion of the treating physician.

After completion of study treatment, patients are followed up at 3 and 6 months.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion

  • Patients must have a Karnofsky performance status of >= 60%; this must be met pre-surgery and pre-study therapy
  • Patients must have histological confirmation of colorectal carcinoma and present with potentially resectable or abatable metachronous or synchronous hepatic metastases
  • Patients must have colorectal tumors that produce CEA as documented by either immunohistochemistry or by an elevated serum CEA
  • Prior radiotherapy, immunotherapy, or chemotherapy must have been completed at least four weeks prior to start of FUdR/RIT therapy on this study (6 weeks if mitomycin-C or nitrosoureas were part of last therapy) and patients must have recovered from all expected side effects of the prior therapy
  • Laboratory values must be met pre-surgery and pre-study therapy
  • Hemoglobin > 10 gm % (patients may be transfused to reach a hemoglobin > 10 gm %)
  • WBC > 4000/ul
  • Absolute granulocyte count of > 1,500/mm^3
  • Platelets > 150,000/ul
  • Patients may have history of prior malignancy for which the patient has been disease-free for five years with the exception of basal or squamous cell skin cancers or carcinoma in situ of the cervix
  • Patients must have no prior history of radiation therapy to the liver
  • Total bilirubin < 1.5 (unless reversibly obstructed due to the metastatic tumor)
  • Serum creatinine of < 2.0
  • Patients must have evidence of intrahepatic metastases involving < 60% of the functioning liver
  • Patients cannot have evidence of extrahepatic disease with the following exceptions: patients known to have a resectable "anastomotic" or local recurrence of their tumor; patients who undergoing their initial surgery for resection of their primary colorectal carcinoma can have potentially resectable porta hepatis and/or mesenteric lymph node involvement in addition to liver metastases; patients who have disease extension from the liver metastasis that can be resected en bloc (e.g., diaphragm, kidney, and abdominal wall); patients who have minimal, potentially resectable to less than 3 cm extrahepatic disease
  • The pre-operative eligibility checklist must be completed
  • If a patient has previously received murine or chimeric antibody, then serum anti-antibody testing must be negative (This must be met pre-surgery if possible)
  • Serum HIV testing and hepatitis B surface antigen and C antibody testing must be negative
  • Women of childbearing potential must have a negative serum pregnancy test prior to entry and while on study must be practicing an effective form of contraception (This must be met pre-surgery and pre-study therapy)
  • Patients must have resectable or abatable liver metastases as determined by the attending surgeon
  • Colorectal carcinoma must be confined to the liver except as noted above
  • Patients with limited extrahepatic disease as defined (primary, lymph node, or anastomotic recurrence) must have disease resected or debulked to less than 3 cm in greatest dimension
  • To receive study therapy, patients must be at least 3 weeks post-surgery but no more than 16 weeks post surgery and without evidence of post-operative complications, such as infection or poor wound healing
  • Patients must have < 40% liver resected at the close of completion of the hepatic resection

Exclusion

  • Patients that have received radiation therapy to greater than 50% of their bone marrow
  • Patients with any nonmalignant intercurrent illness (example cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment or which is of such severity that the investigators deem it unwise to enter the patient on protocol shall be ineligible
  • Biopsy-proven chronic active hepatitis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00645710

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Jeffrey Wong Beckman Research Institute
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00645710     History of Changes
Other Study ID Numbers: 04122, NCI-2010-01229, CDR0000590335
Study First Received: March 27, 2008
Last Updated: November 13, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Gemcitabine
Floxuridine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 20, 2014