Immunotoxin Therapy in Treating Patients With Advanced Cancer

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

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

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

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


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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?
-----------------
Primary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ovarian serous cystadenocarcinoma, recurrent non-small cell lung cancer, stage III cervical cancer, recurrent cervical cancer, stage IVB cervical cancer, stage IVA cervical cancer, squamous cell lung cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, recurrent ovarian epithelial cancer, advanced malignant mesothelioma, recurrent malignant mesothelioma, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent metastatic squamous neck cancer with occult primary, ovarian undifferentiated adenocarcinoma, ovarian mixed epithelial carcinoma, ovarian endometrioid adenocarcinoma, ovarian clear cell cystadenocarcinoma, cervical squamous cell carcinoma, metastatic squamous neck cancer with occult primary squamous cell carcinoma, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, recurrent squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the paranasal sinus and nasal cavity, stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, fallopian tube cancer, primary peritoneal cavity cancer, ovarian carcinosarcoma, Brenner tumor, untreated metastatic squamous neck cancer with occult primary, recurrent salivary gland cancer, salivary gland squamous cell carcinoma, stage III salivary gland cancer, stage IV salivary gland cancer, recurrent pancreatic cancer, stage II pancreatic cancer, stage III pancreatic cancer, ovarian mucinous cystadenocarcinoma, borderline ovarian surface epithelial-stromal tumor, ovarian sarcoma, ovarian stromal cancer, stage IV pancreatic cancer