Ignite Creation Date:
2024-05-05 @ 12:10 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00262327
Status:
UNKNOWN
Last Update Posted:
2006-06-20
First Post:
2005-12-02
Brief Title:
Safety and Efficacy of Adenoviral Endostatin in the Treatment of Advanced Solid Tumor
Sponsor:
Sun Yat-sen University
Organization:
Sun Yat-sen University
Study Overview
Official Title:
Phase I Trial of Intratumoral Injection of an Adenovirus Encoding Human Endostatin for Advanced Solid Tumors
Status:
UNKNOWN
Status Verified Date:
2005-12
Last Known Status:
ACTIVE_NOT_RECRUITING
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 growth and metastasis of solid tumors are dependent on angiogenesis Endostatin the C-terminal proteolytic fragment of collagen XVIII is an effective endogenous angiogenesis inhibitor in cancer therapy in mice Applied for clinical studies in solid tumor however recombinant human endostatin protein difficulties in a large-scale production of the recombinant endostatin protein and the cumbersome daily administration Up to now its clinical application has been hampered by those matters We herein constructed a adenoviral vector ecoding human endostatin This study will test the safety and efficacy of recombinant human endostatin adenovirus Ad-rhE in the treatment of patients with advanced solid tumors
Detailed Description:
It is widely recognized that angiogenesis not only is important in physiological processes such as embryonic development wound healing and organ and tissue regeneration but also play a pivotal role in tumor growth tissue invasion and metastasis1 This complex multistep process of angiogenesis involves interactions between tumor cells and endothelial cells ECs growth factors and extracellular matrix components Tumors that are unable to elicit angiogenesis exist in a dormant state and are unable to grow beyond the size of 1-2 mm Angiogenesis is regulated by a variety of pro-angiogenesis and anti-angiogenesis factors and their imbalance can lead to disease The abnormal features of the tumor vasculature perhaps represent an imbalanced expression of proangiogenic factors and antiangiogenic factors1 Antiangiogenic therapies inhibit the growth of genetically stable endothelial cells and most tumors should starve to death with little acquired resistance Antiangiogenesis agents such as Avastin for the treatment of cancer have now been approved by the FDA in the US and in other countries2 Endostatin a 20 kDa C-terminal fragment of the carboxyterminus of collagen XVIII has been shown to block endothelial cell proliferation survival and migration in part through downregulating proangiogenic factor such as Ids HIF-1a VEGF-A bFGF and upregulating antiangiogenic factors such as Thrombospondin-12 vasostatin kininogen456 Of the endogenous antiangiogenic factors in the body endostatin has broadest anti-cancer spectrum and the least toxic and no resistance anti-cancer drug in mice and human Endostatin is the first endogenous angiogenesis inhibitor to introduce into human clinical trials
However therapy with recombinant endostatin protein is hampered by their shot half-life difficulties in protein production and long-term storage of bioactive protein Furthermore the inhibition of tumor angiogenesis is a long-term and chronic process of treatment Gene therapy may be overcome these difficulties by introducing human endostatin cDNA into the host and using the body as an endogenous factory to generate highly bioactive gene product Expression of endostatin by adenoviral gene transfer Ad-rhEndo E10A generates a strong systemic therapeutic effect in several models of solid tumors in mice78910 Intratumoral injections of E10A into subcutaneous xenografts of hepatocellular carcinoma BEL-7402 nasopharyngeal carcinoma CNE-2 Tongue cancer Tca8113 in nude mice demonstrated significant tumor growth inhibition and reduce angiogenesis in tumors No toxic effects of E10A administration in these pharmacology studies were identified On the base of promising preclinical results in solid tumors we undertook a dose-escalation phase I trial of E10A in the treatment of patients with advanced solid tumors
However therapy with recombinant endostatin protein is hampered by their shot half-life difficulties in protein production and long-term storage of bioactive protein Furthermore the inhibition of tumor angiogenesis is a long-term and chronic process of treatment Gene therapy may be overcome these difficulties by introducing human endostatin cDNA into the host and using the body as an endogenous factory to generate highly bioactive gene product Expression of endostatin by adenoviral gene transfer Ad-rhEndo E10A generates a strong systemic therapeutic effect in several models of solid tumors in mice78910 Intratumoral injections of E10A into subcutaneous xenografts of hepatocellular carcinoma BEL-7402 nasopharyngeal carcinoma CNE-2 Tongue cancer Tca8113 in nude mice demonstrated significant tumor growth inhibition and reduce angiogenesis in tumors No toxic effects of E10A administration in these pharmacology studies were identified On the base of promising preclinical results in solid tumors we undertook a dose-escalation phase I trial of E10A in the treatment of patients with advanced solid tumors
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 |
|---|---|---|---|
| E10A | None | None | None |