Clinical trial NCT00010270: LMB-9 Immunotoxin in Treating Patients With Advanced Pancreatic, Esophageal, Stomach, Colon, or Rectal Cancer
Official title: A Phase I Study Of LMB-9, A Recombinant Disulfide Stabilized Anti-Lewis Y Immonutoxin Administered By 5-Days Continuous Infusion For Patients With Colorectal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Colorectal Cancer
Esophageal Cancer
Gastric Cancer
Pancreatic Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
stage III pancreatic cancer
stage II pancreatic cancer
recurrent pancreatic cancer
adenocarcinoma of the pancreas
stage IV gastric cancer
adenocarcinoma of the stomach
recurrent gastric cancer
adenocarcinoma of the esophagus
stage IV esophageal cancer
stage III esophageal cancer
recurrent esophageal cancer
stage II esophageal cancer
adenocarcinoma of the rectum
stage III colon cancer
stage III rectal cancer
stage III gastric cancer
stage IV pancreatic cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: LMB-9 immunotoxin can locate tumor cells and kill them without harming normal cells. This may be an effective treatment for advanced pancreatic, esophageal, stomach, colon or rectal cancer.

PURPOSE: Phase I trial to study the effectiveness of LMB-9 immunotoxin in treating patients who have advanced pancreatic, esophageal, stomach, colon, or rectal cancer.

Detailed description: OBJECTIVES:

* Determine the toxicity of LMB-9 immunotoxin in patients with advanced adenocarcinoma of the colon, rectum, pancreas, esophagus, or stomach with overexpression of the Lewis-Y antigen.
* Determine the maximum tolerated dose of this drug in these patients.
* Determine the clinical response of patients treated with this drug.
* Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive LMB-9 immunotoxin IV continuously on days 1-5. Patients with stable or responding disease after completion of the first course receive additional courses every 4-5 weeks 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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 weeks and then every 2 months thereafter.

PROJECTED ACCRUAL: A total of 40-50 patients will be accrued for this study within 1-2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed advanced adenocarcinoma of the colon, rectum, pancreas, esophagus, or stomach that is refractory to standard treatment
* Overexpression of the Lewis-Y antigen
* Measurable or evaluable disease
* No CNS metastasis
* Metastatic liver disease from primary tumor allowed

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-1

Life expectancy:

* At least 3 months

Hematopoietic:

* Platelet count greater than 100,000/mm\^3
* Absolute granulocyte count greater than 1,200/mm\^3

Hepatic:

* Bilirubin normal
* SGOT and SGPT no greater than 1.5 times upper limit of normal
* Hepatitis B or C antigen negative
* No liver disease (e.g., alcohol liver disease)
* Albumin at least 3.0 g/dL

Renal:

* Creatinine no greater than 1.4 mg/dL
* Creatinine clearance at least 60 mL/min
* Proteinuria no greater than 1 g/24 hours (grade II toxicity-like)

Cardiovascular:

* No prior coronary artery disease
* No New York Heart Association class II, III, or IV congestive heart failure
* No arrhythmia requiring treatment

Pulmonary:

* FEV_1 and FVC greater than 65% predicted

Other:

* No other concurrent malignancy
* No active peptic ulcer disease
* No known allergy to omeprazole
* No known seizure disorder
* No concurrent medical or psychiatric condition that would preclude study participation
* No contraindication to pressor therapy
* 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 nitrosoureas or mitomycin) 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
Study officials:
affiliation: Kreiskrankenhaus Emmendingen
name: Peter Hafkemeyer, MD
role: STUDY_CHAIR
References: