Immunotoxin Therapy in Treating Patients With Advanced Cancer

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.

Eligibility Criteria:
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