Safety Study of Adenovirus/PNP Coupled With Fludarabine Phosphate to Treat Solid Tumors

Completed · Phase 1

Conditions studied: Head and Neck Cancer

In brief

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 (i.e., 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.

Key facts

Study ID: NCT01310179
Run by: PNP Therapeutics, Inc.
People needed: 12
Starts: 2011-02-01
Expected to finish: 2014-07-01
Last updated by the study team: 2015-06-10

Who can join

Age: 19 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Biopsy confirmed diagnosis of a solid tumor
Failed or exhausted all standard or approved treatment options that would provide substantive palliation
Have at least one measurable primary or metastatic tumor on imaging studies or physical exam whose potential reduction could provide relief of symptoms or benefit
Tumor is accessible for direct intratumoral injection

You may not qualify if…

Diagnosis of leukemia
Have previously received any gene therapy products or oncolytic viral therapy
Receiving treatment with allopurinol
Received radiation treatment < 4 wks prior to first injection of Ad/PNP
Received chemotherapy < 4 wks prior to first injection of Ad/PNP
Have signs or symptoms of active infection
Receiving chronic systemic corticosteroids or any chronic immunosuppressive medications within 14 days prior to first injection of Ad/PNP. Subjects receiving short courses of corticosteroids are considered eligible.

Where it is running

University of Alabama at Birmingham — Birmingham, Alabama, United States
Vanderbilt-Ingram Cancer Center — Nashville, Tennessee, United States

Full record on ClinicalTrials.gov

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