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

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

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.

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.

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