View Clinical Trial (Medical Research Study)
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
| City: |
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Duarte |
| State: |
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California |
| Zip Code: |
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91010 |
| Conditions: |
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Liver Metastases - Recurrent Colon Cancer - Recurrent Rectal Cancer - Stage IV Colon Cancer - Stage IV Rectal Cancer |
| Purpose: |
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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.
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| Study Summary: |
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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.
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| Criteria: |
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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
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| NCT ID: |
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NCT00645710 |
| Primary Contact: |
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Principal Investigator
Jeffrey Wong
Beckman Research Institute
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| Backup Contact: |
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N/A |
| Location Contact: |
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Duarte, California 91010
United States
Jeffrey Y. Wong
Phone: 800-826-4673
Email: jwong@coh.org
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 25, 2013 |
| Modifications to this listing: |
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