Gene Therapy for Pleural Malignancies

A Phase I Clinical Trial of Repeated Dose Intrapleural Adenoviral-Mediated Interferon-beta (BG00001, Ad.hIFN-β for Pleural Malignancies

This Phase I study will evaluate the safety of two doses of BG00001 at different doses and intervals. Eligible subjects will have:

• malignant pleural mesothelioma, or
• pleural effusions who have progressed through at least one prior therapy or have refused therapy

BG00001 is given twice through a catheter in the pleural space.

Ad.hIFN-β (BG00001) is a replication-defective recombinant adenoviral vector containing the human interferon-beta (hIFN-β) gene. This Phase I study is designed to evaluate the safety and maximum tolerated dose (MTD) of two doses of intrapleural (IP) Ad.hIFN-β in subjects with pleural malignancies either metastatic or pleural mesothelioma.

Five dose levels will be studied:

• Dose levels 1, 2, and 3 will be given on Days 1 and 15
• Dose levels 4 and 5 will be given on Days 1 and 8

Inclusion Criteria:

• must have malignant pleural effusion from mesothelioma or metastatic from primary lung, breast, gastrointestinal, genitourinary, melanoma, or sarcoma
• must have evaluable disease
• must have ECOG performance status of 2
• must have pleural space involved with tumor accessible for pleural catheter
• must have FEV1 > 1 liter or 40% of predicted value
• must have completed radiotherapy and/or treatment with chemotherapy, cytotoxic, or immunologic agents 4 weeks prior to dosing with BG00001
• concurrent Tarceva is allowed if patients has been on a stable dose for at least three months and has not had serious adverse events
• patients on stable dose of hormone may continue use of hormone
• patients on stable dose of Tarceva for 3 months and without complications may remain on Tarceva

Exclusion Criteria:

• malignant pleural effusions secondary to lymphoma
• rapidly re-accumulating, symptomatic malignant pleural effusions that require immediate mechanical or chemical pleurodesis for palliation
• untreated brain metastases
• use of concurrent systemic steroids or immunosuppressants