Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00169000
Status:
COMPLETED
Last Update Posted:
2009-08-06
First Post:
2005-09-09
Brief Title:
Safety Study of a New Schedule of Capecitabine and Docetaxel to Treat Cancers
Sponsor:
Dartmouth-Hitchcock Medical Center
Organization:
Dartmouth-Hitchcock Medical Center
Study Overview
Official Title:
Phase I Study of a Novel Schedule of Capecitabine and Docetaxel in Patients With Advanced Solid Tumors
Status:
COMPLETED
Status Verified Date:
2009-08
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:
The combination of capecitabine and docetaxel is given to treat several different types of cancer Capecitabine is usually given by mouth for 14 days and docetaxel is given IV on the first day of capecitabine The effects of changes in the schedule of the combination of docetaxel and capecitabine has been examined in human breast cancer cells A capecitabine by-product was given orally to breast cancer-bearing animals for 14 consecutive days Docetaxel was given IV at a variety of times between days 1 and 15 The greatest reductions in the volume of the cancer were seen when animals were treated with docetaxel between days 6 and 10 In two other breast cancer models the maximal degree of delay in growth of the tumors was achieved when the animals were treated with docetaxel on day 8 of a 14 day course of capecitabine The extent of tumor response was not explained by changes in tumor levels of the enzyme thymidine phosphorylase which is thought to be the mechanism behind the interaction of capecitabine and docetaxel In the breast cancer cells capecitabine increases the level of proteins which promote death of cancer cells and it inhibits the levels of proteins which block death of cancer cells
Our hypothesis is that capecitabine and docetaxel interact with each other because capecitabine primes the pro-death machinery of the cell by increasing the ratio of death-promoting proteins to death-inhibiting proteins Cells are more susceptible to killing by docetaxel when the pro-death machinery is activated by capecitabine
This is a safety study to find the highest dose of capecitabine that can be given safely for 14 days in combination with docetaxel given at a fixed dose on day 8 Once this dose of capecitabine has been determined an additional nine patients with tumors that can be biopsied will be treated at this dose and levels of capecitabine its byproducts and docetaxel will be measured in the bloodstream Biopsies of tumors will also be taken before and after the docetaxel is given and the levels of pro-death and anti-death proteins will be measured
Our hypothesis is that capecitabine and docetaxel interact with each other because capecitabine primes the pro-death machinery of the cell by increasing the ratio of death-promoting proteins to death-inhibiting proteins Cells are more susceptible to killing by docetaxel when the pro-death machinery is activated by capecitabine
This is a safety study to find the highest dose of capecitabine that can be given safely for 14 days in combination with docetaxel given at a fixed dose on day 8 Once this dose of capecitabine has been determined an additional nine patients with tumors that can be biopsied will be treated at this dose and levels of capecitabine its byproducts and docetaxel will be measured in the bloodstream Biopsies of tumors will also be taken before and after the docetaxel is given and the levels of pro-death and anti-death proteins will be measured
Detailed Description:
This is a phase I study using an accelerated titration design to determine the maximum tolerated dose MTD of capecitabine given orally on a BID schedule from days 1-14 in combination with docetaxel given at a fixed dose of 75 mgm2 IV on day 8 Once the MTD of capecitabine has been determined an additional nine patients with accessible tumors will be treated at the MTD Pharmacokinetics of plasma capecitabine 5-FU 5-deoxy-5-fluorouridine and docetaxel will be assayed in these nine patients and tumor biopsies will be taken to assess BaxBcl-2 ratios and Bcl-2 phosphorylation at several time points The primary aim of this study will be to determine the maximum tolerated dose and dose limiting toxicities of capecitabine when given with a fixed dose of docetaxel on day 8 of a 21 day schedule Secondary aims will include assessment of the pharmacokinetics of capecitabine and docetaxel on this schedule and determination of intratumoral BaxBcl-2 Bcl-2 phosphorylation and DPD expression and correlation with clinical toxicities and antitumor response
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