Intrapleural BG00001 in Treating Patients With Malignant Pleural Mesothelioma or Malignant Pleural Effusions

Sponsor

Abramson Cancer Center of the University of Pennsylvania (Other)

Overall Status

Completed

CT.gov ID

NCT00066404

Collaborator

National Cancer Institute (NCI) (NIH)

Location

33.1

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Using BG00001 to insert the gene for interferon-beta into a person's pleural cavity may improve the body's ability to fight cancer.

PURPOSE: Phase I trial to study the effectiveness of intrapleural BG00001 in treating patients who have malignant pleural mesothelioma or malignant pleural effusions.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Biological: recombinant adenovirus-hIFN-beta	Phase 1

Detailed Description

OBJECTIVES:

Determine the safety and toxicity of intrapleural BG00001 in patients with malignant pleural mesothelioma or malignant pleural effusions.
Determine the maximum tolerated dose of this drug in these patients.
Determine the success of gene transfer/interferon beta gene expression in patients treated with this drug.
Determine systemic and intrapleural cytokine responses and cellular and humoral immune response in patients treated with this drug.
Determine, preliminarily, tumor response in patients treated with this drug.

OUTLINE: This is a dose-escalation study.

Patients receive BG00001 via an intrapleural catheter on day 1.

Cohorts of 3-6 patients receive escalating doses of BG00001 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.

Patients are followed weekly for 1 month, biweekly for 1 month, monthly for 4 months, and then every 6 months for 15 years.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase I Clinical Trial of Intrapleural Adenoviral-Mediated Interferon-beta (IFN-ß) Gene Transfer for Pleural Malignancies

Study Start Date :

Apr 1, 2003

Actual Primary Completion Date :

Jan 1, 2006

Actual Study Completion Date :

Jan 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

One of the following histologically or cytologically confirmed diagnoses:
Malignant pleural mesothelioma
Metastatic malignancy to the pleural space
Originating from 1 of the following sites:
Lung
Breast
Gastrointestinal organs
Genitourinary organs
Malignant melanoma
Failed prior standard therapy comprising chemotherapy, radiotherapy, and/or hormonal therapy
Measurable or evaluable disease
Pleural space involved with tumor accessible for pleural catheter insertion
No malignant pleural effusions secondary to lymphoma or sarcoma
No rapidly re-accumulating, symptomatic pleural effusions after thoracentesis or pleural catheter insertion that require immediate mechanical or chemical pleurodesis
No known brain metastases
Previously treated brain metastases with no evidence of active growth are allowed
Hormone receptor status:
Not specified

PATIENT CHARACTERISTICS:

Age

18 and over

Sex

Male or female

Menopausal status

Not specified

Performance status

ECOG 0-1

Life expectancy

Not specified

Hematopoietic

Granulocyte count at least 2,000/mm^3
Platelet count at least 100,000/mm^3
Hematocrit at least 30% (transfusion allowed)

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
ALT and AST no greater than 1.5 times ULN
Alkaline phosphatase no greater than 1.5 times ULN
PT and PTT no greater than 1.5 times normal
No end-stage liver disease
No chronic active hepatitis B (hepatitis B surface antigen negative)

Renal

Creatinine no greater than 2.0 mg/dL
No end-stage renal disease

Cardiovascular

No unstable angina

Pulmonary

FEV_1 greater than 50% of predicted (post-pleural drainage)
No severe oxygen-dependent chronic obstructive pulmonary disease

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No documented immunodeficiency
No other malignancy within the past 5 years except nonmelanoma skin cancer or successfully treated localized malignancy of the bladder or prostate gland with no evidence of active disease
No other life-threatening illness
No known hypersensitivity to any component of study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

More than 4 weeks since prior biologic therapy
No prior bone marrow transplantation, including stem cells
No immunological drugs during and for at least 2 months after study therapy

Chemotherapy

See Disease Characteristics
No chemotherapy during and for at least 2 months after study therapy

Endocrine therapy

See Disease Characteristics
Concurrent hormonal therapy allowed if maintained at dose received prior to study entry
No concurrent steroids

Radiotherapy

See Disease Characteristics
More than 4 weeks since prior radiotherapy
No radiotherapy during and for at least 2 months after study therapy

Surgery

At least 2 weeks since prior surgery

Other

More than 4 weeks since prior cytotoxic agents
No concurrent immunosuppressives or medication that can directly or indirectly suppress the immune system
No other concurrent experimental therapies for pleural cancer