Ignite Creation Date:
2024-05-05 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00079014
Status:
COMPLETED
Last Update Posted:
2013-05-16
First Post:
2004-03-08
Brief Title:
3-AP and Doxorubicin In Treating Patients With Metastatic or Refractory Solid Tumors
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase I Study of Triapine in Combination With Doxorubicin in Refractory Tumors
Status:
COMPLETED
Status Verified Date:
2013-05
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 phase I trial is studying the side effects and best dose of 3-AP and doxorubicin in treating patients with metastatic or refractory solid tumors Drugs used in chemotherapy such as doxorubicin work in different ways to stop tumor cells from dividing so they stop growing or die 3-AP may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth and may help doxorubicin kill more cancer cells by making them more sensitive to the drug
Detailed Description:
PRIMARY OBJECTIVES
I To find the maximal tolerated dose for the combination of doxorubicin and Triapine in patients with refractory solid tumors
SECONDARY OBJECTIVES
I To find the severity and frequency of toxicity associated with this combination and to observe for and record any antitumor activity
TERTIARY OBJECTIVES
I To evaluate the effect of Triapinedoxorubicin on the ribonucleotide reductase tyrosyl radical in vivo by EPR spectroscopy in buccal mucosal cells peripheral blood lymphocytes and in tumor biopsies Formation of low molecular weight iron-Triapine chelates will also be assessed by EPR
II To evaluate the effect of Triapinedoxorubicin on cell cycle in vivo by measuring S-phase arrest in buccal mucosal cells
III To evaluate the effect of Triapinedoxorubicin on MDR gene expression and polymorphisms in blood
IV To evaluate the effect of Triapinedoxorubicin on ribonucleotide reductase R2 mRNA and immunohistochemistry
V To evaluate the pharmacokinetic profile of the combination VI To measure the formulation of circulating isoprostanes as an indicator of oxidative stress with this combination
OUTLINE This is a dose-escalation study of 3-AP Triapine
Patients receive doxorubicin IV over 15 minutes on day 1 and 3-AP Triapine IV over 2 hours on days 1-4 Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of 3-AP Triapine until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity Once the MTD is determined an additional 6 patients are treated at that dose level
Patients are followed until disease progression
I To find the maximal tolerated dose for the combination of doxorubicin and Triapine in patients with refractory solid tumors
SECONDARY OBJECTIVES
I To find the severity and frequency of toxicity associated with this combination and to observe for and record any antitumor activity
TERTIARY OBJECTIVES
I To evaluate the effect of Triapinedoxorubicin on the ribonucleotide reductase tyrosyl radical in vivo by EPR spectroscopy in buccal mucosal cells peripheral blood lymphocytes and in tumor biopsies Formation of low molecular weight iron-Triapine chelates will also be assessed by EPR
II To evaluate the effect of Triapinedoxorubicin on cell cycle in vivo by measuring S-phase arrest in buccal mucosal cells
III To evaluate the effect of Triapinedoxorubicin on MDR gene expression and polymorphisms in blood
IV To evaluate the effect of Triapinedoxorubicin on ribonucleotide reductase R2 mRNA and immunohistochemistry
V To evaluate the pharmacokinetic profile of the combination VI To measure the formulation of circulating isoprostanes as an indicator of oxidative stress with this combination
OUTLINE This is a dose-escalation study of 3-AP Triapine
Patients receive doxorubicin IV over 15 minutes on day 1 and 3-AP Triapine IV over 2 hours on days 1-4 Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of 3-AP Triapine until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity Once the MTD is determined an additional 6 patients are treated at that dose level
Patients are followed until disease progression
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 |
|---|---|---|---|
| CO 03904 | None | None | None |
| WCCC-CO-03904 | None | None | None |
| NCI-6266 | None | None | None |
| P30CA014520 | NIH | None | None |
| U01CA062491 | NIH | None | httpsreporternihgovquickSearchU01CA062491 |