A Phase II Study of the Rate of Conversion to Complete Resection in Patients With Initially Inoperable Hepatic-Only Metastases From Colorectal Cancer After Treatment With Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Best Systemic Chemotherapy
- Assess the rate of conversion to complete resection in patients with initially
unresectable colorectal cancer metastatic to the liver treated with hepatic arterial
infusion comprising floxuridine and dexamethasone in combination with systemic
irinotecan hydrochloride and either oxaliplatin or leucovorin calcium/fluorouracil.
- Evaluate the time to progression in patients treated with this regimen.
- Evaluate disease-free survival of patients treated with this regimen.
- Evaluate overall survival of patients treated with this regimen.
- Determine the response rate (complete, partial, and moderate response) in patients
treated with this regimen.
- Evaluate the safety profile and tolerability of this regimen in these patients.
- Assess the expression pattern of the VEGF receptor VEGFR1, VEGFR2, and VEGFR3 and their
cognate ligands (i.e., VEGF-A, VEGF-B, VEGF-C, VEGF-D, and P1GF) in patients treated
with this regimen.
- Correlate circulating angiogenic markers with tumor resectability, disease progression,
and patient survival.
- Procure normal and diseased liver tissue for evaluation of thymidylate synthase, p53
gene, p21, topoisomerase 1, dihydropyrimidine dehydrogenase, and excision repair
cross-complementing gene levels.
- Assess the expression pattern of tissue factor (TF) and explore its correlation with
the TF receptors PAR-1, PAR-2, TF regulators PTEN, k-ras, b- raf, p53, and
outcome.(Closed as of 11/30/10)
- Assess the prognostic and predictive role of preoperative, pretreatment, and during
treatment serum TF in regards to outcome (progression-free survival and overall
survival) and response to treatment with this regimen and to salvage treatments such as
EGFR-inhibitors.(Closed as of 11/30/10)
OUTLINE: This is an open-label, nonrandomized study. Patients are assigned to 1 of 2
treatment groups according to receipt of more than 2 prior courses of oxaliplatin (no vs
- Group 1 (no more than 2 prior courses of oxaliplatin): Patients receive hepatic
arterial infusion (HAI) therapy comprising floxuridine and dexamethasone continuously
on days 1-14. Patients also receive oxaliplatin IV over 2 hours and irinotecan
hydrochloride IV over 30 minutes on days 1 and 15. Courses repeat every 4 weeks in the
absence of disease progression or unacceptable toxicity.
- Group 2 (more than 2 prior courses of oxaliplatin): Patients receive HAI therapy as in
group 1. Patients also receive irinotecan hydrochloride IV over 30 minutes and
leucovorin calcium IV over 30 minutes on days 1 and 15 and fluorouracil IV continuously
over 48 hours on days 1, 2, 15, and 16. Courses repeat every 4 weeks in the absence of
disease progression or unacceptable toxicity.
In both groups, patients may undergo complete resection of liver metastases after completion
of at least 3 courses of therapy.
Some patients undergo blood and tissue collection periodically for correlative and
immunological studies. Samples are analyzed for VEGF receptor VEGFR1, VEGFR2, VEGFR3,
thymidylate synthase, p53, p21, topoisomerase 1, dihydropyrimidine dehydrogenase, and
excision repair cross-complementing gene levels.
After completion of study treatment, patients are followed every 3 months for 2 years, every
4 months for 3 years, and then annually thereafter.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Michael D'Angelica, MD
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|Memoral Sloan Kettering Cancer Center||Basking Ridge, New Jersey|
|Memorial Sloan-Kettering Cancer Center @ Suffolk||Commack, New York 11725|
|Memoral Sloan Kettering Cancer Center@Phelps Memorial Hospital||Sleepy Hollow, New York|
|Memorial Sloan-Kettering at Mercy Medical Center||Rockville Centre, New York|