Clinical trial NCT00155558: A Phase I Trial of HDFL48 in Recurrent or Metastatic Colorectal Cancers
Official title: A Phase I Trial of HDFL48(Weekly 48-Hour Infusion of High-Dose 5-Fluorouracil and Leucovorin) in Recurrent or Metastatic Colorectal Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Recurrent or Metastatic Colorectal Cancer
Keywords: Colorectal Cancer, Maximum tolerated dose
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2005-09-12
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: To determine the maximum tolerated dose and dose limiting toxicity
timeFrame: 2000~2005
Secondary outcomes:
measure: response
timeFrame: 2000~2005
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Department of Oncology, National Taiwan University hospital
Study officials:
affiliation: Department of Oncology, National Taiwan University hospital
name: Kun-Huei Yeh, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: