LMB-9 Immunotoxin in Treating Patients With Advanced Colon, Breast, Non-small Cell Lung, Bladder, Pancreatic, or Ovarian Cancer

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of LMB-9 immunotoxin in treating patients who have advanced colon, breast, non-small cell lung, bladder, pancreatic, or ovarian cancer. The LMB-9 immunotoxin can locate tumor cells and kill them without harming normal cells.

Detailed Description
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OBJECTIVES: I. Determine the maximum tolerated dose of LMB-9 immunotoxin in patients with advanced colon, breast, non-small cell lung, bladder, pancreas, or ovarian cancer. II. Assess the toxicity and pharmacokinetics of this treatment regimen in these patients. III. 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.

Official Title
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Phase I Study of LMB-9, a Recombinant Disulfide Stabilized Anti-Lewis Y Immunotoxin Admistered by Continuous Infusion

Conditions
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Ovarian Cancer, Bladder Cancer, Breast Cancer, Colorectal Cancer, Lung Cancer, Pancreatic Cancer

Intervention / Treatment
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* Biological: LMB-9 immunotoxin


Participation Criteria
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Eligibility Criteria
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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 PATIENT CHARACTERISTICS: Age: 18 and over Sex: Male or female 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: 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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Biological: LMB-9 immunotoxin<br> <br> |

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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stage III colon cancer, stage IV colon cancer, stage IV breast cancer, stage IIIA breast cancer, recurrent breast cancer, stage IIIB breast cancer, recurrent non-small cell lung cancer, stage II pancreatic cancer, stage III pancreatic cancer, recurrent pancreatic cancer, recurrent colon cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, recurrent ovarian epithelial cancer, stage III bladder cancer, recurrent bladder cancer, stage IV bladder cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, ovarian stromal cancer, stage III ovarian germ cell tumor, stage IV ovarian germ cell tumor, recurrent ovarian germ cell tumor, borderline ovarian surface epithelial-stromal tumor, ovarian sarcoma, male breast cancer, stage IV pancreatic cancer