Clinical trial NCT00006046: Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer
Official title: Phase I Study of Humanized 3S193 (Anti-Lewis-Y) Antibody in Patients With Advanced Colorectal Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Lead sponsor: Ludwig Institute for Cancer Research
Sponsor class: OTHER
First posted: 2003-05-21
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced colorectal cancer.

Detailed description: OBJECTIVES:

* Determine the toxicity, maximum tolerated dose, and pharmacokinetics of monoclonal antibody hu3S193 in patients with advanced colorectal carcinoma.
* Determine the immune response in these patients treated with this regimen.

OUTLINE: This is a dose escalation study.

Patients receive monoclonal antibody hu3S193 (mAb hu3S193) IV over 30 minutes to 4 hours weekly for 8 weeks followed by 2 weeks of rest. Patients with stable or responding disease at week 10 receive maintenance mAb hu3S193 weekly. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of mAb hu3S193 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose limiting toxicities.

Eligibility criteria: Inclusion Criteria:

* Histologically proven stage IV colorectal carcinoma.
* Failed or refused conventional chemotherapy.
* Lewis Y antigen present on more than 50% of tumor cells.
* Measurable or evaluable disease.
* No central nervous system (CNS) tumor involvement.
* Karnofsky 80-100%.
* Life expectancy: At least 6 weeks.
* Granulocyte count greater than 1,500/mm\^3.
* Platelet count greater than 100,000/mm\^3.
* Bilirubin no greater than 1.0 mg/dL.
* Prothrombin time less than 3 times upper limit of normal.
* Creatinine no greater than 1.4 mg/dL.
* Female patients of childbearing age and male patients must be asked to use effective contraception during the study.
* At least 4 weeks since other prior immunotherapy. Exclusion Criteria
* New York Heart Association class III or IV heart disease.
* Serious infection requiring antibiotics or other serious illness.
* Pregnancy or nursing.
* History of bleeding gastric ulcers or pancreatitis.
* Diabetes mellitus requiring insulin.
* Human antimouse antibodies (HAMA).
* No prior mouse monoclonal antibody or antibody fragments.
* Illness requiring the use of steroids or other anti-inflammatory agents.
* Positive anti-hu3S193 antibody (HAHA) titer.

Primary outcomes:
measure: Number of Patients With Dose-limiting Toxicities (DLTs)
timeFrame: up to 10 weeks.
Secondary outcomes:
measure: Number of Patients With Tumor Responses
timeFrame: 8 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Sydney Welt, MD
role: STUDY_CHAIR
References: