Clinical trial NCT00299962: Gene Therapy for Pleural Malignancies
Official title: A Phase I Clinical Trial of Repeated Dose Intrapleural Adenoviral-Mediated Interferon-beta (BG00001, Ad.hIFN-β for Pleural Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pleural Mesothelioma
Metastatic Pleural Effusions
Keywords: gene therapy
immunotherapy
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Biogen
First posted: 2006-03-07
Enrollment: 17
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 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

Eligibility criteria: 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

Primary outcomes:
measure: To determine toxicity of two doses of intrapleural BG00001 (Ad.hIFN-β over 8 days, and
timeFrame: Through Day 85
Secondary outcomes:
measure: To assess systemic and intrapleural cytokine responses as well as cellular and humoral immune responses after repeated BG00001 instillation,
timeFrame: Through Day 85
measure: and to assess, in a preliminary way, efficacy via tumor regression, time to progression and survival.
timeFrame: 15 years or until subject dies, whichever comes first
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Daniel H. Sterman, M.D.
role: PRINCIPAL_INVESTIGATOR
References: