Ignite Creation Date:
2024-05-05 @ 11:21 PM
Last Modification Date:
2024-10-26 @ 10:32 AM
Study NCT ID:
NCT01310179
Status:
COMPLETED
Last Update Posted:
2015-06-10
First Post:
2011-03-03
Brief Title:
Safety Study of AdenovirusPNP Coupled With Fludarabine Phosphate to Treat Solid Tumors
Sponsor:
PNP Therapeutics Inc
Organization:
PNP Therapeutics Inc
Study Overview
Official Title:
Phase I Open-label Study Evaluating the Safety of Escalating Doses of AdPNP-F-araAMP AdPNP Administered Intratumorally With Co-administration of Fludarabine Phosphate Intravenously in Subjects With Advanced Solid Tumors
Status:
COMPLETED
Status Verified Date:
2015-05
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 study will test whether it is possible to introduce new genetic material into a small portion of a tumor and have the product of the new gene not only kill those tumor cells that were infected initially but also the surrounding tumor cells as well with limited or no harm to the patient The desired effects of this approach are achieved by focusing potent chemotherapies directly within the tumor itself and as a result avoiding injury to the remainder of the body In this study we will use two components the first of which is a virus known as an adenovirus that has been crippled ie it cannot make more of itself and loaded with a bacterial gene called E coli purine nucleoside phosphorylase PNP Adenoviruses are considered to be relatively safe vehicles for gene delivery and are presently being used in numerous human trials and therapies worldwide including a head and neck cancer therapy approved for use outside the United States The loaded adenovirus will be used to deliver the PNP gene directly into a tumor in patients This gene is not expected to have an effect itself However the gene produces PNP inside the tumor and this protein will activate the second component of the therapy a drug called fludarabine phosphate which is approved by the FDA for certain types of blood-cell cancers but has not been shown to be effective against most solid tumors The proposed therapy gives the patient several infusions of fludarabine following the injection of the virus carrying the PNP gene and as the fludarabine enters the tumor it will be converted by PNP into a second compound fluoroadenine Numerous studies in mice and rats have shown that fluoroadenine is a very potent anti-cancer agent and that it will kill the tumor cells where it is made as well as those in the immediately surrounding area
Detailed Description:
For this first study we will inject the PNP-loaded adenovirus into the tumors of patients with cancers primarily in the throat and neck and then give them the drug This study is designed with two goals in mind 1 assessing the overall safety of this approach for the patient and 2 observing the effects of this anti-cancer strategy on the tumor itself This will be accomplished in two parts First we will introduce a modest fixed amount of the gene-carrying adenovirus into the tumors of three separate groups of patients and then administer small increasingly strong amounts of the fludarabine phosphate to each successive group over a three-day period Even in the group that will receive the highest amount of fludarabine the total amount given to any individual patient over those three days will be significantly less than the dose approved by the FDA for patients with non-solid tumors Finally a more concentrated amount of the adenovirus approximately 10 times more viruses will be given to a fourth group of patients who will also receive the highest dose of the drug that was shown to be well tolerated in the prior three groups the highest dose at which no serious problems were observed
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