A Phase I Trial of HDFL48 in Recurrent or Metastatic Colorectal Cancers

Study Overview
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Brief Summary
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To determine the maximum tolerated dose and dose limiting toxicity of 5-FU and leucovorin with novel 48-hour infusion schedule, and to collect toxicity profile at different dose level of 5-FU/LV 48-hour infusion.

Detailed Description
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Colorectal cancer is one of the major in Taiwan.It caused 3128 deaths in 1999, and represented the No.3 cancer killer in both male and female population of Taiwan. Recently, evidence has accumulated that weekly, 24-hour infusion of high-dose 5-FU may improve the response rate and survival time compared with 5-FU bolus regiment. In a randomized multicenter trial of metastatic colorectal cancer, Kohne et al reported an overall response rate of 44%and a median survival time of 16 months using a weekly-times-six schedule of infusional 5-FU (2600mg/m2 24-hours infusion). In another randomized study for advanced colorectal cancer, de Gramont et al reported a significantly better outcome in patients treated by a similar schedule which combined bolus plus infusional 5-FU compared to bolus 5-FU. These results suggest that 24-or 48-hour infusion of high-dose 5-FU is more effective than the conventional bolus schedules.

Official Title
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A Phase I Trial of HDFL48(Weekly 48-Hour Infusion of High-Dose 5-Fluorouracil and Leucovorin) in Recurrent or Metastatic Colorectal Cancers

Conditions
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Recurrent or Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: 5-Fluorouracil, Leucovorin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed recurrent or metastatic colorectal adenocarcinoma Patients are indicated for 5-FU (1st-line after recurrence/metastasis), OR have failed 5-FU ,treatment with other schedules At least one bi-dimensionally measurable lesion(s) Previous C/T, R/T >= 4 weeks KPS > 50% Age >= 18 years Fasting TG > 70 mg/dL (within 7 days) WBC >= 3,000/uL or ANC >= 1,500/uL Plt >= 75,000/uL Cre<= 1.5 mg/dL Proteinuria < 1+ Normal T-bil AST/ ALT <= 3.5-fold of ULN Exclusion Criteria: Concomitant anticancer therapy or radiotherapy CNS metastasis Pregnant women Patients who have second malignancy Symptomatic heart disease (significant arrhythmia, CHF or MI within 3 months of entry) Active infection exists Extensive liver disease or liver cirrhosis Patients who refuse Port-A catheter implantation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: 5-Fluorouracil, Leucovorin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the maximum tolerated dose and dose limiting toxicity |  | 2000 2005 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response |  | 2000 2005 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal Cancer, Maximum tolerated dose