A Pilot And Feasibility Trial Evaluating Two Different Chemotherapy Regimens In Combination With Intrapleural Adenoviral-Mediated Interferon-Alpha Gene Transfer For Malignant Pleural Mesothelioma
Malignant pleural mesothelioma (MPM) is a cancer for which there is no cure. The most
effective combination chemotherapy, Pemetrexed (Alimta)/Cisplatin, has yielded overall
response rates of up to 40%, but with improvements in overall median survival of only 3.5
months. Prior Phase I trials of intrapleural infusion (IP) of Ad.hIFN-beta (BG00001) were
safe. The most recent trial of IP Ad.IFNalpha (SCH 721015) at a dose of 3e11 viral particles
(vp) given three days apart was safe and well tolerated, and showed high levels of IFN in
pleural fluid and serum. Our preclinical data modeling this proposed study suggest that two
IP doses of Ad.IFN-alpha in combination with chemotherapy are well tolerated and markedly
enhances efficacy. The purpose of the new study is to determine the safety of administrating
intrapleural SCH 721015 (Ad.hIFN-alpha 2b) in combination with chemotherapy for the
management of malignant pleural mesothelioma. This study will enroll subjects with pleural
mesothelioma. Subjects will receive two fixed dosed of SCH 721015 followed by 4-6 cycles of
chemotherapy. Subjects will require placement of a pleural catheter for administration of
Some patients require a pleural catheter for control of pleural fluid while some will have
it placed for research purpose only. Protocol participation will last about 6 months the
subjects will be followed up by telephone every 6 months for 15 years.
Primary Purpose: Treatment
To determine the safety of administering intrapleural SCH 721015, Ad.hIFN-alpha2b (Adenoviral-mediated Interferon-alpha) in combination with chemotherapy for the management of MPM.
No dose escalation is planned; however, dose de-escalation is possible should two or more DLTs be encountered in the first six patients treated. With 0 DLTs in 6 patients at a given dose, the upper exact 90% confidence limit on the DLT rate is 32%. With 1 DLT in 6 patients, the Bayesian upper 90% probability limit on the DLT rate is 58%. With 10 subjects per treatment group, we can identify with 90% power any unanticipated toxicity that has prevalence at least 20.6%; with n=15 per group, this figure decreases to 14.2%.
Daniel H Sterman, MD
Abramson Cancer Center of the University of Pennsylvania
United States: Food and Drug Administration
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