Clinical trial NCT00005858: LMB-9 Immunotoxin in Treating Patients With Advanced Colon, Breast, Non-small Cell Lung, Bladder, Pancreatic, or Ovarian Cancer
Official title: Phase I Study of LMB-9, a Recombinant Disulfide Stabilized Anti-Lewis Y Immunotoxin Admistered by Continuous Infusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bladder Cancer
Breast Cancer
Colorectal Cancer
Lung Cancer
Ovarian Cancer
Pancreatic Cancer
Keywords: 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
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Judith E. Karp, MD
role: STUDY_CHAIR
References: