Gene Therapy for Pleural Malignancies

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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Pleural Mesothelioma, Metastatic Pleural Effusions

Intervention / Treatment
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* Biological: Adenoviral-mediated Interferon-beta
* Biological: SCH 721015


Participation Criteria
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Eligibility Criteria
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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

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 4<br> | Biological: Adenoviral-mediated Interferon-beta<br>* BG00001 at doses 1.5 x 10e12 and 3 x 10e12 viral particles Days 1 and 8<br>Biological: SCH 721015<br>* Comparison of different doses and frequency of investigational agent<br>* Other names: Ad.hIFN-beta;|
| Experimental: Dose level 5<br> | Biological: Adenoviral-mediated Interferon-beta<br>* BG00001 at doses 1.5 x 10e12 and 3 x 10e12 viral particles Days 1 and 8<br>Biological: SCH 721015<br>* Comparison of different doses and frequency of investigational agent<br>* Other names: Ad.hIFN-beta;|
| Experimental: Dose Level 1<br>on Days 1 and 15 | Biological: SCH 721015<br>* Comparison of different doses and frequency of investigational agent<br>* Other names: Ad.hIFN-beta;|
| Experimental: Dose Level 2<br>On Days 1 and 15 | Biological: SCH 721015<br>* Comparison of different doses and frequency of investigational agent<br>* Other names: Ad.hIFN-beta;|
| Experimental: Dose Level 3<br>On Days 1 and 15 | Biological: SCH 721015<br>* Comparison of different doses and frequency of investigational agent<br>* Other names: Ad.hIFN-beta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine toxicity of two doses of intrapleural BG00001 (Ad.hIFN-β over 8 days, and |  | Through Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess systemic and intrapleural cytokine responses as well as cellular and humoral immune responses after repeated BG00001 instillation, |  | Through Day 85 | 
| and to assess, in a preliminary way, efficacy via tumor regression, time to progression and survival. |  | 15 years or until subject dies, whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gene therapy, immunotherapy