LMB-9 Immunotoxin in Treating Patients With Advanced Solid Tumors

Phase I Study of LMB-9, a Recombinant Disulfide Stabilized Immunotoxin for Advanced Carcinomas That Express Lewis Y Antigen

RATIONALE: The LMB-9 immunotoxin may be able to locate tumor cells and kill them without harming normal cells. This may be an effective treatment for advanced solid tumors.

PURPOSE: Phase I trial to study the effectiveness of LMB-9 immunotoxin in treating patients who have advanced solid tumors that have not responded to standard therapy.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Esophageal Cancer; Lung Cancer; Bladder Cancer
• Intervention / Treatment: Biological: LMB-9 immunotoxin

Detailed Description

OBJECTIVES: I. Determine the toxic effects and the pharmacokinetics of LMB-9 immunotoxin in patients with advanced solid tumors that express Lewis Y antigen. II. Evaluate the anti-tumor activity and the immunogenicity of this treatment regimen in these patients.

OUTLINE: This is a dose-escalation study. Patients receive LMB-9 immunotoxin IV over 30 minutes on days 1, 3, and 5. Patients with negative neutralizing antibody to LMB-9 immunotoxin with stable or responding disease receive additional courses every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of LMB-9 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. Once the MTD is determined, an additional cohort of 6 patients may be treated at the MTD. Patients are followed at 1 month and then every 2 months thereafter.

PROJECTED ACCRUAL: Approximately 20-30 patients will be accrued within 12-24 months.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Medicine Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced solid tumor refractory to standard treatment or for which no effective standard therapy exists Bladder cancer Breast cancer Colon cancer Esophageal cancer Gastric cancer Non-small cell lung cancer Pancreatic cancer Evaluable or measurable disease B3 antigen present on more than 30% of tumor cells No prior or concurrent CNS metastasis Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: 18 and over Menopausal status: Not specified Performance status: ECOG 0-1 Life expectancy: At least 3 months Hematopoietic: Granulocyte count greater than 1,200/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin normal SGOT/SGPT less than 5 times upper limit of normal Albumin at least 3.0 g/dL No history of liver disease No positive hepatitis B or C antigen Renal: Creatinine no greater than 1.4 mg/dL Cardiovascular: No history of coronary artery disease No New York Association class II-IV heart disease No arrhythmia requiring treatment No contraindications to pressor therapy Pulmonary: FEV1 and FVC greater than 65% of predicted value Pulmonary function test required of patients with significant smoking history or possible pulmonary disease Other: No active peptic ulcer disease No known allergy to omeprazole No history of seizure disorders No other concurrent malignancy No concurrent medical or psychiatric condition that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 3 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosourea) and recovered Endocrine therapy: At least 3 weeks since prior hormonal therapy Radiotherapy: At least 3 weeks since prior radiotherapy and recovered Surgery: Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Study Chair: Ira Pastan, MD, National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: May 1, 1998

Study Registration Dates

• First Submitted: July 11, 2001
• First Submitted That Met QC Criteria: May 5, 2003
• First Posted (Estimate): May 6, 2003

Study Record Updates

• Last Update Posted (Estimate): April 29, 2015
• Last Update Submitted That Met QC Criteria: April 28, 2015
• Last Verified: April 1, 2007

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; recurrent non-small cell lung cancer; recurrent bladder cancer; stage IV bladder cancer; stage IV non-small cell lung cancer; stage IV colon cancer; recurrent colon cancer; recurrent pancreatic cancer; stage IV pancreatic cancer; stage IV gastric cancer; recurrent gastric cancer; recurrent esophageal cancer; stage IV esophageal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Endocrine System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Head and Neck Neoplasms; Esophageal Diseases; Pancreatic Diseases; Stomach Neoplasms; Breast Neoplasms; Lung Neoplasms; Urinary Bladder Neoplasms; Pancreatic Neoplasms; Esophageal Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunotoxins
• Other Study ID Numbers: CDR0000066180; NCI-98-C-0078A; NCI-MB-400; NCI-T98-0005