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

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Completed

CT.gov ID

NCT00005858

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Actual Duration (Months)

12.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Breast Cancer Colorectal Cancer Lung Cancer Ovarian Cancer Pancreatic Cancer	Biological: LMB-9 immunotoxin	Phase 1

Detailed Description

OBJECTIVES:

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

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 1, 2000

Actual Primary Completion Date :

Dec 1, 2003

Actual Study Completion Date :

Dec 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I 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

Arm

Intervention/Treatment

Experimental: Arm I

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
2	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182