Immunotoxin Therapy in Treating Patients With Advanced Cancer

Phase I Study Of SS1(dsFv)-PE38 (SS1P) Anti-Mesothelin Immunotoxin in Advanced Malignancies: Continuous Infusion X 10 Days

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be an effective treatment for advanced cancer.

PURPOSE: Phase I trial to study the effectiveness of immunotoxins in treating patients who have advanced cancer.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and toxic effects of SS1(dsFv)-PE38 immunotoxin in patients with advanced malignancies that express mesothelin.

Secondary

• Determine the response in patients treated with this drug.
• Determine the plasma pharmacokinetics of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive SS1(dsFv)-PE38 immunotoxin IV continuously on days 1-10. Treatment repeats every 4 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SS1(dsFv)-PE38 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy, including one of the following:

  • Malignant mesothelioma

  • Ovarian epithelial carcinoma (mucinous or nonmucinous), including primary peritoneal or fallopian tube carcinoma

    • Tumors that may have originated in the bowel (e.g., appendiceal carcinoma) and involve the ovary
    • Ovarian cancers of other histology are eligible provided they express mesothelin

  • Pancreatic cancer

  • Squamous cell lung cancer

  • Squamous cell cancer of the head and neck

  • Squamous cell cancer of the cervix

• Recurrent unresectable disease after prior standard anticancer therapy that was expected to prolong survival and improve quality of life OR unwilling to receive standard anticancer therapy

• At least 30% of initial or recurrent tumor cells positive (at least 1+) for mesothelin by immunohistochemistry

• Measurable or evaluable disease

• No known CNS or spinal cord involvement

• No clinically significant pericardial effusion

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 75,000/mm^3

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN
• Albumin at least 3.0 g/dL
• Hepatitis B and C negative

Renal:

• Creatinine no greater than ULN OR
• Creatinine no greater than 2.0 mg/dL if creatinine clearance at least 50 mL/min
• Calcium no greater than ULN

Cardiovascular:

• No New York Heart Association class II-IV heart disease

Pulmonary:

• Oxygen saturation (SO_2) more than 92% on room air

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No detectable antibody to SS1(dsFv)-PE38
• No infection requiring parenteral antibiotics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior hematopoietic growth factor therapy

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• At least 4 weeks since any prior antitumor therapy and recovered
• No other concurrent antitumor therapy