Ignite Creation Date:
2024-05-05 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001579
Status:
COMPLETED
Last Update Posted:
2006-07-17
First Post:
1999-11-03
Brief Title:
A Phase I Trial of 5-Fluorouracil Given With 776C85 GW776 and Low-Dose Leucovorin in Adult Patients With Solid Tumors
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase I Trial of 5-Fluorouracil Given With 776C85 GW776 and Low-Dose Leucovorin in Adult Patients With Solid Tumors
Status:
COMPLETED
Status Verified Date:
2000-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a dose escalation study
During the first period of this study an initial pharmacological assessment of fluorouracil administered intravenously along with oral leucovorin calcium is made Leucovorin calcium is given orally bid on days 1-3 Fluorouracil is given as a 24 hour infusion on day 2
After a 2 week rest period and resolution of any toxicities experienced during the first period of treatment patients are given an escalating dose of fluorouracil with fixed doses of leucovorin calcium and ethynyluracil Ethynyluracil and leucovorin calcium are given bid orally on days 1-3 of each week Fluorouracil is given bid orally on day 2 of each week Treatment is repeated for three weeks followed by a one week rest period
3 to 6 patients are enrolled at each dose level Dose escalation proceeds until the maximum tolerated dose MTD is determined MTD is defined as the dose preceding that at which 2 or more patients experience dose limiting toxicity
During the first period of this study an initial pharmacological assessment of fluorouracil administered intravenously along with oral leucovorin calcium is made Leucovorin calcium is given orally bid on days 1-3 Fluorouracil is given as a 24 hour infusion on day 2
After a 2 week rest period and resolution of any toxicities experienced during the first period of treatment patients are given an escalating dose of fluorouracil with fixed doses of leucovorin calcium and ethynyluracil Ethynyluracil and leucovorin calcium are given bid orally on days 1-3 of each week Fluorouracil is given bid orally on day 2 of each week Treatment is repeated for three weeks followed by a one week rest period
3 to 6 patients are enrolled at each dose level Dose escalation proceeds until the maximum tolerated dose MTD is determined MTD is defined as the dose preceding that at which 2 or more patients experience dose limiting toxicity
Detailed Description:
The primary purpose of this Phase I protocol is to develop an orally administered regimen of fluorouracil 5-FU given with fixed doses of leucovorin LV and 776C85 GW776 a mechanism-based inhibitor of dihydropyrimidine dehydrogenase DPD the rate-limiting enzyme involved in the catabolism of 5-FU In the presence of 776C85 5-FU is cleared by renal mechanisms The schedule employed is intended to mimic the pharmacologic profile associated with a 24 hour weekly continuous infusion of 5-FU without the need for an indwelling central venous catheter The target population is adult cancer patients with solid tumors
The first week each patient will receive a single dose of 5-FU given by 24 hour continuous IV infusion at its recommended Phase II dose with low-dose oral LV In the third week the patient will begin 776C85 GW776 and LV PO on days 1 2 3 at fixed doses Oral 5-FU will be given on day 2 and the dose will be escalated in successive cohorts of patients Treatment will be repeated weekly for three weeks followed by a one week break The dose of 5-FU will be adjusted according to individual tolerance Cohorts of three patients will be entered at each dose level of 5-FU which will be escalated until dose-limiting toxicity is seen guidelines are outlined in the following schema Treatment will be continued indefinitely until evidence of disease progression provided the patient is tolerating therapy and wishes to continue
Biochemical monitoring suggests that there is profound and sustained inhibition of DPD with a single dose of 20 mg PO 776C85 days 1-3 each week for three of four weeks Once the MTD has been defined for the once daily dosing on days 1 2 3 schedule a simplified schedule will be evaluated in which a single dose of 776C85 on day 1 in the evening with oral leucovorin days 1 and 2 and 5-FU given day 2 as a single dose
Since the pharmaceutical company has decided to go with a combined tablet of eniluracil5-FU for future studies the new schedule will be oral leucovorin on days 1 2 with 776C85 and 5-FU both given day 2 as a single dose
The first week each patient will receive a single dose of 5-FU given by 24 hour continuous IV infusion at its recommended Phase II dose with low-dose oral LV In the third week the patient will begin 776C85 GW776 and LV PO on days 1 2 3 at fixed doses Oral 5-FU will be given on day 2 and the dose will be escalated in successive cohorts of patients Treatment will be repeated weekly for three weeks followed by a one week break The dose of 5-FU will be adjusted according to individual tolerance Cohorts of three patients will be entered at each dose level of 5-FU which will be escalated until dose-limiting toxicity is seen guidelines are outlined in the following schema Treatment will be continued indefinitely until evidence of disease progression provided the patient is tolerating therapy and wishes to continue
Biochemical monitoring suggests that there is profound and sustained inhibition of DPD with a single dose of 20 mg PO 776C85 days 1-3 each week for three of four weeks Once the MTD has been defined for the once daily dosing on days 1 2 3 schedule a simplified schedule will be evaluated in which a single dose of 776C85 on day 1 in the evening with oral leucovorin days 1 and 2 and 5-FU given day 2 as a single dose
Since the pharmaceutical company has decided to go with a combined tablet of eniluracil5-FU for future studies the new schedule will be oral leucovorin on days 1 2 with 776C85 and 5-FU both given day 2 as a single dose
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 97-C-0136 | None | None | None |