Intrapleural Gene Transfer for Pleural Mesothelioma

Ad.hIFN-α (SCH 721015, adenoviral-mediated interferon alpha) is a replication-defective recombinant adenoviral vector containing the human interferon-alpha (hIFN-alpha) gene. This Phase I study is designed to evaluate the safety and maximum tolerated dose (MTD) of two doses of Ad.hIFN-alpha injected into the pleural (intrapleural, IP) and given 4 days apart in subjects with pleural mesothelioma.

Subjects who meet eligibility will have a pleural catheter placed 2 weeks prior to the first dose. Subjects are then admitted to the research center on Days 1 and 4 for dosing and overnight observation. Subjects are then followed-up as outpatients for a total of 6 months. Radiographic evaluations are repeated on Day 64 and at 6 months. The pleural catheter is removed once it is not necessary.

Inclusion criteria

• evidence of progressive disease after standard first line treatment of mesothelioma; OR patient has refused standard first line treatment of mesothelioma
• evaluable disease
• No radiotherapy and/or treatment with chemotherapeutic, cytotoxic, or immunologic agents within 14 days prior to infusion of the IFN-α vector
• Must have a pleural space involved with tumor accessible for pleural catheter insertion
• FEV1> 1 liter or 40% of predicted value
• Must have an anti-adenoviral neutralizing antibody titer equal to or less than 1:1000. This will be measured by the Penn Vector Core

Exclusion criteria

• Presence of HIV or Hepatitis B infection
• Use of concurrent systemic steroids, immunosuppressives, or any other medications that can directly or indirectly suppress the immune system
• Presence of any other life-threatening illness, such as unstable angina, severe oxygen dependence, significant chronic obstructive pulmonary disease (COPD), end stage liver or renal disease
• Presence of untreated brain metastases
• Prior bone marrow or stem cell transplants