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

NCT ID: NCT00005858

Last Updated: 2019-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-04-30
• Study Completion Date: 2003-12-31

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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

LMB-9 immunotoxin

Intervention Type: BIOLOGICAL

Interventions

LMB-9 immunotoxin

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith E. Karp, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Marlene and Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Countries

United States

Other Identifiers

CDR0000067885

Identifier Type: REGISTRY

Identifier Source: secondary_id

MSGCC-IRB-0200123

Identifier Type: -

Identifier Source: secondary_id

NCI-511

Identifier Type: -

Identifier Source: secondary_id

MSGCC-9981

Identifier Type: -

Identifier Source: org_study_id