Clinical trial NCT01212367: Intrapleural Gene Transfer for Pleural Mesothelioma
Official title: A Pilot Study of Repeated Dose Intrapleural Adenoviral-Mediated Interferon-Alpha (SCH 721015, Ad.hIFN-a2b) Gene Transfer for Malignant Pleural Mesothelioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Pleural Mesothelioma
Keywords: Gene transfer
Immunology
Cancer
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-09-30
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research will study how to activate the immune system by using gene transfer. Gene transfer involves inserting a specially designed gene into cancer cells. A gene is a part of the genetic code that instructs the cells of our bodies to produce specific compounds (proteins) important for the makeup or function of the cell. The study hypothesis is that repeated doses of SCH 721015 given over a three day interval would result in gene transfer.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: To analyze gene transfer with two does separated by three-day interval
timeFrame: After the first dose and at each visit until day 94
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Daniel Sterman
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sterman DH, Haas A, Moon E, Recio A, Schwed D, Vachani A, Katz SI, Gillespie CT, Cheng G, Sun J, Papasavvas E, Montaner LJ, Heitjan DF, Litzky L, Friedberg J, Culligan M, June CH, Carroll RG, Albelda SM. A trial of intrapleural adenoviral-mediated Interferon-alpha2b gene transfer for malignant pleural mesothelioma. Am J Respir Crit Care Med. 2011 Dec 15;184(12):1395-9. doi: 10.1164/rccm.201103-0554CR. Epub 2011 Jun 3.