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

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).

Inclusion criteria

• 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

Exclusion criteria

• 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.