Liver MetastasesPhase 1/2NCT00645710
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
A Phase 1/2 study testing gemcitabine hydrochloride, floxuridine and proteomic profiling in people with Liver Metastases and Recurrent Colon Cancer, run by City of Hope Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Metastases, Recurrent Colon Cancer, Recurrent Rectal Cancer
- What is being tested?
- gemcitabine hydrochloride, floxuridine and proteomic profiling
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jun 2005to 7 Feb 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 %)
Show all 24Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
OBJECTIVES:
- 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.
- 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.
- Conditions
- Liver Metastases, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer
- Being tested
- gemcitabine hydrochloride, floxuridine, proteomic profiling, matrix-assisted laser desorption/ionization time of flight mass spectrometry, liquid chromatography
- Medical subject headings
- Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called dFdC, dFdCyd, difluorodeoxycytidine hydrochloride, gemcitabine
Given IV
floxuridineDrug
Also called 5-FUDR, FdUrD, floxuridin, fluorodeoxyuridine
Given via hepatic arterial infusion
proteomic profilingGenetic
Correlative studies
matrix-assisted laser desorption/ionization time of flight mass spectrometryOther
Also called MALDI-TOF Mass Spectrometry
Correlative studies
liquid chromatographyOther
Also called LC
Correlative studies
yttrium Y 90 anti-CEA monoclonal antibody cT84.66Radiation
Given IV
laboratory biomarker analysisOther
Correlative studies
mass spectrometryOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With at Least One Dose Limiting Toxicity
Dose Limiting Toxicity (DLT) defined as any treatment-related grade grade 3 nonhematologic toxicity not reversible to grade 2 or less within 24 hours, or any grade 4 toxicity.Up to three cycles of therapy were allowed with DLTs determined based on first cycle tolerance. Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2.0.
Measured: 4 weeks from start of treatment, up to 2 years.
Recommended Phase II Dose
The maximum tolerated dose (MTD) of HAI FUdR in combination with intravenous gemcitabine and 90Y-DTPA-cT84.66 is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.
Measured: 4 weeks from start of treatment, up to 2 years.
Secondary outcomes (2)
Overall Survival
Estimated using the product-limit method of Kaplan and Meier. Event defined as death due to any cause.
Measured: Up to 5 years
Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression is defined as a 25% increase in the sum of products of measurable lesions over the smallest sum observed, or appearance of any lesions that had disappeared, or appearance of any new lesion/site.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2008 (estimated)
- Study start13 Jun 2005
- Primary completion7 Feb 2018
- Study completion7 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Liver MetastasesStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey Wong, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00645710
- Sponsor's protocol ID
- 04122
- Other IDs
- NCI-2010-01229, CDR0000590335
- Status last verified
- Oct 2026
- First submitted
- 27 Mar 2008
- Last updated
- 3 Nov 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00645710
- Acronym / sponsor ID
- 04122
- Conditions
- Liver Metastases, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Study start
- 13 Jun 2005 (actual)
- Primary completion
- 7 Feb 2018 (actual)
- Study completion
- 7 Feb 2018 (actual)
- First posted
- 28 Mar 2008 (estimated)
- Results
- Posted 28 Mar 2019
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 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.
Detailed description
OBJECTIVES:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | 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 studyPatients 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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
Key exclusion criteria (3 listed)
- 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
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 |
|---|---|---|
| gemcitabine hydrochlorideAlso: dFdC, dFdCyd, difluorodeoxycytidine hydrochloride, gemcitabineGiven IV | Drug | Arm I |
| floxuridineAlso: 5-FUDR, FdUrD, floxuridin, fluorodeoxyuridineGiven via hepatic arterial infusion | Drug | Arm I |
| proteomic profilingCorrelative studies | Genetic | Arm I |
| matrix-assisted laser desorption/ionization time of flight mass spectrometryAlso: MALDI-TOF Mass SpectrometryCorrelative studies | Other | Arm I |
| liquid chromatographyAlso: LCCorrelative studies | Other | Arm I |
| yttrium Y 90 anti-CEA monoclonal antibody cT84.66Given IV | Radiation | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
| mass spectrometryCorrelative studies | Other | Arm I |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I |
Primary outcome
Number of Participants With at Least One Dose Limiting Toxicity
Time frame: 4 weeks from start of treatment, up to 2 years.
Dose Limiting Toxicity (DLT) defined as any treatment-related grade grade 3 nonhematologic toxicity not reversible to grade 2 or less within 24 hours, or any grade 4 toxicity.Up to three cycles of therapy were allowed with DLTs determined based on first cycle tolerance. Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2.0.
Recommended Phase II Dose
Time frame: 4 weeks from start of treatment, up to 2 years.
The maximum tolerated dose (MTD) of HAI FUdR in combination with intravenous gemcitabine and 90Y-DTPA-cT84.66 is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.
2 secondary outcomes
Overall Survival
Time frame: Up to 5 years
Progression-free Survival
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jeffrey Wong 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 1/2 study testing gemcitabine hydrochloride, floxuridine and proteomic profiling in people with Liver Metastases and Recurrent Colon 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 24 inclusion and 3 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 3 Nov 2026. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With at Least One Dose Limiting Toxicity (time frame: 4 weeks from start of treatment, up to 2 years.). The study lists 2 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 3 Nov 2026.