Immunotoxin Therapy in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be effective in treating advanced solid tumors. PURPOSE: This phase I trial is studying the side effects and best dose of immunotoxin therapy in treating patients with recurrent unresectable advanced solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of SS1(dsFv)-PE38 immunotoxin in patients with advanced mesothelin-expressing malignancies. Secondary Determine the toxic effects of this drug in these patients. Determine the plasma pharmacokinetics of this drug in these patients. Determine the response in patients treated with this drug. Correlate the induction of antibody against this drug with its pharmacokinetics in these patients. OUTLINE: This is an open-label, dose-escalation study. Patients receive a test dose of SS1(dsFv)-PE38 immunotoxin IV over 1-2 minutes on day 1 followed by SS1(dsFv)-PE38 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 4 weeks for up to 3 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 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 3-15 patients will be accrued for this study.

Official Title
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Phase I Study Of SS1(dsFv)-PE38 Anti-Mesothelin Immunotoxin In Advanced Malignancies: I.V. Infusion QOD Dosing

Conditions
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Cervical Cancer, Fallopian Tube Cancer, Head and Neck Cancer, Lung Cancer, Malignant Mesothelioma, Ovarian Cancer, Pancreatic Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Biological: SS1(dsFv)-PE38 immunotoxin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed advanced malignancy of 1 of the following types: Ovarian cancer All nonmucinous epithelial histologies are eligible Primary peritoneal cavity cancer Fallopian tube cancer Malignant mesothelioma No sarcomatous histology Pancreatic cancer Squamous cell cancer (SCC) of the lung SCC of the cervix SCC of the head and neck Recurrent unresectable disease, meeting 1 of the following criteria: Previously treated with definitive standard therapy Patient refused prior standard therapy Initial or recurrent tumor positive (at least 30% of tumor cells) for mesothelin by immunohistochemistry* NOTE: *Immunohistochemical evaluation not required for patients with pancreatic cancer Measurable or evaluable disease No clinically significant pericardial effusion No known CNS or spinal cord involvement by tumor PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count at least 1,500/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 Seropositive allowed if clinically asymptomatic except if clinically asymptomatic and bilirubin and AST and ALT meet the outlined criteria Renal Creatinine no greater than ULN Calcium no greater than ULN Cardiovascular No New York Heart Association class II-IV cardiovascular disease Pulmonary Oxygen saturation at least 93% on room air DLCO at least 50% of predicted* Total lung capacity and vital capacity at least 50% of predicted* FEV_1 at least 50% of predicted* NOTE: *For patients with pleural mesothelioma and as clinically indicated Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No infection requiring parenteral antibiotics No HIV infection Serum neutralizing activity to SS1(dsFv)-PE38 immunotoxin (at 200 ng/mL) no greater than 75% PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other At least 4 weeks since prior therapy and recovered No other concurrent antitumor therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: SS1(dsFv)-PE38 immunotoxin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian carcinosarcoma, ovarian clear cell cystadenocarcinoma, ovarian endometrioid adenocarcinoma, ovarian mixed epithelial carcinoma, ovarian serous cystadenocarcinoma, ovarian undifferentiated adenocarcinoma, recurrent ovarian epithelial cancer, Brenner tumor, primary peritoneal cavity cancer, fallopian tube cancer, epithelial mesothelioma, recurrent malignant mesothelioma, recurrent pancreatic cancer, cervical squamous cell carcinoma, recurrent cervical cancer, recurrent non-small cell lung cancer, squamous cell lung cancer, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent metastatic squamous neck cancer with occult primary, recurrent salivary gland cancer, salivary gland squamous cell carcinoma, recurrent squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the nasopharynx