Intrapleural Gene Transfer for Pleural Mesothelioma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Pilot Study of Repeated Dose Intrapleural Adenoviral-Mediated Interferon-Alpha (SCH 721015, Ad.hIFN-a2b) Gene Transfer for Malignant Pleural Mesothelioma

Conditions
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Malignant Pleural Mesothelioma

Intervention / Treatment
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* Biological: SCH 721015
* Biological: SCH 721015


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1<br> | Biological: SCH 721015<br>* 1.0 x 10e12 viral particles on Days 1 and 4<br>* Other names: Ad.IFN-alpha;|
| Experimental: Dose Level 2<br>This is a dose de escalation. | Biological: SCH 721015<br>* 3.0 x 10e11 viral particles on Days 1 and 4<br>* Other names: Ad.IFN-alpha;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To analyze gene transfer with two does separated by three-day interval |  | After the first dose and at each visit until day 94 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene transfer, Immunology, Cancer