OBJECTIVES:

• Determine the maximum tolerated dose of LMB-9 immunotoxin in patients with advanced colon, breast, non-small cell lung, bladder, pancreas, or ovarian cancer.
• Assess the toxicity and pharmacokinetics of this treatment regimen in these patients.
• Determine the clinical responses in patients treated with this regimen.

OUTLINE: This is a dose-escalation study.

Patients receive LMB-9 immunotoxin IV continuously for 10 days. Treatment continues every 30 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of LMB-9 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 weeks and then every 2 months thereafter.

PROJECTED ACCRUAL: A total of 3-25 patients will be accrued for this study within 12-24 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced colon, breast, non-small cell lung, bladder, pancreas, or ovarian cancer refractory to standard treatment or for which no effective standard therapy exists
• Expresses Lewis Y antigen
• Evidence of disease progression
• B3 antigen on the surface of more than 30% of the tumor cells determined by immunohistochemistry
• No neutralizing antibodies to LMB-9 immunotoxin
• No untreated CNS metastases

• 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:

• At least 3 months

Hematopoietic:

• Absolute granulocyte count greater than 1,200/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times normal
• SGOT and SGPT no greater than 2.5 times upper limit of normal (liver metastases allowed)
• Albumin at least 3.0 g/dL
• No prior liver disease (e.g., alcohol liver disease)
• Hepatitis B and C negative

Renal:

• Creatinine no greater than 1.4 mg/dL
• Creatinine clearance greater than 60 mL/min
• Proteinuria less than 1 g/24 hours

Cardiovascular:

• No history of coronary artery disease
• No cardiac arrhythmia requiring therapy
• No New York Heart Association class II-IV congestive heart failure

Pulmonary:

• Pulmonary function test required if significant smoking history, possible pulmonary disease, or lung cancer
• FEV1 and FVC at least 65% predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known seizure disorders
• No urinary tract infection
• No other concurrent malignancy
• No active peptic ulcer disease
• No known allergy to omeprazole
• No contraindication to pressor therapy
• No other concurrent medical or psychological condition that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered

Endocrine therapy:

• At least 3 weeks since prior hormonal therapy

Radiotherapy:

• At least 3 weeks since prior radiotherapy and recovered

Surgery:

• Not specified