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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005858
First received: June 2, 2000
Last updated: February 8, 2013
Last verified: March 2003
  Purpose

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 Intervention Phase
Bladder Cancer
Breast Cancer
Colorectal Cancer
Lung Cancer
Ovarian Cancer
Pancreatic Cancer
Biological: LMB-9 immunotoxin
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Enrollment: 25
Study Start Date: April 2000
Primary Completion Date: April 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005858

Locations
United States, Maryland
Marlene and Stewart Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, United States, 21201
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Judith E. Karp, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005858     History of Changes
Other Study ID Numbers: CDR0000067885, MSGCC-9981, MSGCC-IRB-0200123, NCI-511
Study First Received: June 2, 2000
Last Updated: February 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Breast Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Ovarian Neoplasms
Pancreatic Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Breast Diseases
Skin Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on July 24, 2014