Gene Therapy for Pleural Malignancies

Phase 1

Completed

• Conditions: Metastatic Pleural Effusions; Pleural Mesothelioma
• Interventions: Biological: Adenoviral-mediated Interferon-beta; Biological: SCH 721015

• Registration Number: NCT00299962
• Lead Sponsor: University of Pennsylvania

Brief Summary

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

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

Study Timeline

• Study Start: 2006-03
• Study First Submitted: 2006-03-03
• Study First Submitted QC: 2006-03-03
• Study First Posted: 2006-03-07
• Primary Completion: 2008-05
• Study Completion: 2009-10
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-16
• Last Update Posted: 2020-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose level 4	SCH 721015	-
Dose level 5	Adenoviral-mediated Interferon-beta	-
Dose level 5	SCH 721015	-
Dose Level 1	SCH 721015	on Days 1 and 15
Dose Level 2	SCH 721015	On Days 1 and 15
Dose level 4	Adenoviral-mediated Interferon-beta	-
Dose Level 3	SCH 721015	On Days 1 and 15

Primary Outcome Measures

Name	Time	Method
To determine toxicity of two doses of intrapleural BG00001 (Ad.hIFN-β over 8 days, and	Through Day 85

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States