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

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 malignantpleural effusions.

Study Type: Interventional
Study Design: Treatment

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.

Eligibility

Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both

Criteria

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

Location and Contact Information

Pennsylvania

Abramson Cancer Center at University of Pennsylvania Medical Center Philadelphia, Pennsylvania, 19104, United States; Recruiting
Adri Recio, RN 215-573-6760

Study chairs or principal investigators

Daniel H. Sterman, MD, Study Chair, University of Pennsylvania Cancer Center

*** POSTED JULY, 2003 ***