Ignite Creation Date:
2024-05-05 @ 11:42 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00117013
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2005-06-30
Brief Title:
A Pilot Trial of Oral Topotecan for the Treatment of Refractory Advanced Solid Neoplasms Expressing HIF-1a
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Trial of Oral Topotecan for the Treatment of Refractory Advanced Solid Neoplasms Expressing HIF-1 Alpha
Status:
COMPLETED
Status Verified Date:
2011-08-25
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:
Background
HIF-1 is a common mediator of hypoxic and non-hypoxic pathways that affects a transcriptional program leading to survival angiogenesis migration and invasion of cancer cells We have demonstrated that chronic administration of topotecan inhibits HIF-1alpha expression angiogenesis and tumor growth in human xenografts Notably the mechanism by which topotecan inhibits HIF-1alpha protein expression is independent of replication-mediated DNA damage suggested a mechanism of action distinct from its cytotoxic effects
Objectives
This clinical trial is designed to explore the hypothesis that chronic administration of topotecan TPT inhibits Hypoxia Inducible factor 1alpha HIF-1alpha expression and angiogenesis in patients with metastatic tumors over-expressing HIF-1alpha
Eligibility
Adult patients with metastatic solid tumors expressing HIF-1alpha for whom standard therapy does not exist or would likely not be effective will be evaluated for study eligibility Due to safety concerns pregnant women and HIV-infected individuals are excluded from this study Prior to enrollment archival tumor tissue wil be evaluated for the expression of HIF-1alpha as assessed by IHC Only patients who have tumors that express HIF-1alpha and who meet all eligibility criteria will be enrolled on this study Patients will be asked to undergo a biopsy to evaluate HIF-1alpha expression before starting treatment and at the end of treatment on cycle 2 day 12 or 13 cycle 2
Design
Topotecan at the dose of 12 mgm2 will be administered orally daily x 5 for 2 weeks during a 28 days cycle Imaging studies including CT FDG-PET and DCE-MRI will be performed at baseline at the end of treatment on cycle 1 day 9 or 10 end of treatment on cycle 2 day 12 or 13 and then every 2 cycles and will provide information on clinical response as well as tumor metabolism and angiogenesis The repeat scans on day 9 or 10 of cycle 1 will be performed solely for research purposes to evaluate for early changes in tumor metabolism and angiogenesis Additional correlative studies include evaluation of mRNA expression of HIF-1 target genes in tumor tissue circulating markers of angiogenesis and measurement of circulating endothelial precursor cells CEP The goal of this trial is to establish whether topotecan inhibits HIF-1alpha and angiogenesis in human cancers
HIF-1 is a common mediator of hypoxic and non-hypoxic pathways that affects a transcriptional program leading to survival angiogenesis migration and invasion of cancer cells We have demonstrated that chronic administration of topotecan inhibits HIF-1alpha expression angiogenesis and tumor growth in human xenografts Notably the mechanism by which topotecan inhibits HIF-1alpha protein expression is independent of replication-mediated DNA damage suggested a mechanism of action distinct from its cytotoxic effects
Objectives
This clinical trial is designed to explore the hypothesis that chronic administration of topotecan TPT inhibits Hypoxia Inducible factor 1alpha HIF-1alpha expression and angiogenesis in patients with metastatic tumors over-expressing HIF-1alpha
Eligibility
Adult patients with metastatic solid tumors expressing HIF-1alpha for whom standard therapy does not exist or would likely not be effective will be evaluated for study eligibility Due to safety concerns pregnant women and HIV-infected individuals are excluded from this study Prior to enrollment archival tumor tissue wil be evaluated for the expression of HIF-1alpha as assessed by IHC Only patients who have tumors that express HIF-1alpha and who meet all eligibility criteria will be enrolled on this study Patients will be asked to undergo a biopsy to evaluate HIF-1alpha expression before starting treatment and at the end of treatment on cycle 2 day 12 or 13 cycle 2
Design
Topotecan at the dose of 12 mgm2 will be administered orally daily x 5 for 2 weeks during a 28 days cycle Imaging studies including CT FDG-PET and DCE-MRI will be performed at baseline at the end of treatment on cycle 1 day 9 or 10 end of treatment on cycle 2 day 12 or 13 and then every 2 cycles and will provide information on clinical response as well as tumor metabolism and angiogenesis The repeat scans on day 9 or 10 of cycle 1 will be performed solely for research purposes to evaluate for early changes in tumor metabolism and angiogenesis Additional correlative studies include evaluation of mRNA expression of HIF-1 target genes in tumor tissue circulating markers of angiogenesis and measurement of circulating endothelial precursor cells CEP The goal of this trial is to establish whether topotecan inhibits HIF-1alpha and angiogenesis in human cancers
Detailed Description:
Background
HIF-1 is a common mediator of hypoxic and non-hypoxic pathways that affects a transcriptional program leading to survival angiogenesis migration and invasion of cancer cells We have demonstrated that chronic administration of topotecan inhibits HIF-1alpha expression angiogenesis and tumor growth in human xenografts Notably the mechanism by which topotecan inhibits HIF-1alpha protein expression is independent of replication-mediated DNA damage suggested a mechanism of action distinct from its cytotoxic effects
Objectives
This clinical trial is designed to explore the hypothesis that chronic administration of topotecan TPT inhibits Hypoxia Inducible factor 1alpha HIF-1alpha expression and angiogenesis in patients with metastatic tumors over-expressing HIF-1alpha
Eligibility
Adult patients with metastatic solid tumors expressing HIF-1alpha for whom standard therapy does not exist or would likely not be effective will be evaluated for study eligibility Due to safety concerns pregnant women and HIV-infected individuals are excluded from this study Prior to enrollment archival tumor tissue wil be evaluated for the expression of HIF-1alpha as assessed by IHC Only patients who have tumors that express HIF-1alpha and who meet all eligibility criteria will be enrolled on this study Patients will be asked to undergo a biopsy to evaluate HIF-1alpha expression before starting treatment and at the end of treatment on cycle 2 day 12 or 13 cycle 2
Design
Topotecan at the dose of 12 mgm2 will be administered orally daily x 5 for 2 weeks during a 28 days cycle Imaging studies including CT and DCE-MRI will be performed at baseline at the end of treatment on cycle 1 day 9 or 10 end of treatment on cycle 2 day 12 or 13 and will provide information on clinical response as well as tumor angiogenesis The repeat scans on day 9 or 10 of cycle 1 will be performed solely for research purposes to evaluate for early changes in tumor angiogenesis Additional correlative studies include evaluation of mRNA expression of HIF-1 target genes in tumor tissue circulating markers of angiogenesis and measurement of circulating endothelial precursor cells CEP The goal of this trial is to establish whether topotecan inhibits HIF-1alpha and angiogenesis in human cancers
HIF-1 is a common mediator of hypoxic and non-hypoxic pathways that affects a transcriptional program leading to survival angiogenesis migration and invasion of cancer cells We have demonstrated that chronic administration of topotecan inhibits HIF-1alpha expression angiogenesis and tumor growth in human xenografts Notably the mechanism by which topotecan inhibits HIF-1alpha protein expression is independent of replication-mediated DNA damage suggested a mechanism of action distinct from its cytotoxic effects
Objectives
This clinical trial is designed to explore the hypothesis that chronic administration of topotecan TPT inhibits Hypoxia Inducible factor 1alpha HIF-1alpha expression and angiogenesis in patients with metastatic tumors over-expressing HIF-1alpha
Eligibility
Adult patients with metastatic solid tumors expressing HIF-1alpha for whom standard therapy does not exist or would likely not be effective will be evaluated for study eligibility Due to safety concerns pregnant women and HIV-infected individuals are excluded from this study Prior to enrollment archival tumor tissue wil be evaluated for the expression of HIF-1alpha as assessed by IHC Only patients who have tumors that express HIF-1alpha and who meet all eligibility criteria will be enrolled on this study Patients will be asked to undergo a biopsy to evaluate HIF-1alpha expression before starting treatment and at the end of treatment on cycle 2 day 12 or 13 cycle 2
Design
Topotecan at the dose of 12 mgm2 will be administered orally daily x 5 for 2 weeks during a 28 days cycle Imaging studies including CT and DCE-MRI will be performed at baseline at the end of treatment on cycle 1 day 9 or 10 end of treatment on cycle 2 day 12 or 13 and will provide information on clinical response as well as tumor angiogenesis The repeat scans on day 9 or 10 of cycle 1 will be performed solely for research purposes to evaluate for early changes in tumor angiogenesis Additional correlative studies include evaluation of mRNA expression of HIF-1 target genes in tumor tissue circulating markers of angiogenesis and measurement of circulating endothelial precursor cells CEP The goal of this trial is to establish whether topotecan inhibits HIF-1alpha and angiogenesis in human cancers
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 |
|---|---|---|---|
| 05-C-0186 | None | None | None |