Gene Therapy for Pleural Malignancies

University of Pennsylvania

Status and phase: Completed; Phase 1

Conditions: Pleural Mesothelioma; Metastatic Pleural Effusions

Treatments: Biological: Adenoviral-mediated Interferon-beta; Biological: SCH 721015

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00299962

803776

P01CA066726 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 5 patient groups

Dose level 4

Experimental group

Treatment:

Biological: SCH 721015

Biological: Adenoviral-mediated Interferon-beta

Dose level 5

Experimental group

Treatment:

Biological: SCH 721015

Biological: Adenoviral-mediated Interferon-beta

Dose Level 1

Experimental group

Description:

on Days 1 and 15

Treatment:

Biological: SCH 721015

Dose Level 2

Experimental group

Description:

On Days 1 and 15

Treatment:

Biological: SCH 721015

Dose Level 3

Experimental group

Description:

On Days 1 and 15

Treatment:

Biological: SCH 721015