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

University of Maryland Baltimore (UMB)

Status and phase: Completed; Phase 1

Conditions: Breast Cancer; Bladder Cancer; Lung Cancer; Ovarian Cancer; Pancreatic Cancer; Colorectal Cancer

Treatments: Biological: LMB-9 immunotoxin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00005858

CDR0000067885 (Registry Identifier)

MSGCC-9981

NCI-511

MSGCC-IRB-0200123

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Arm I

Experimental group

Description:

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.

Treatment:

Biological: LMB-9 immunotoxin