Monoclonal Antibody Therapy in Treating Patients Scheduled for Surgery to Remove Ovarian Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Giving monoclonal antibodies in different ways may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have ovarian cancer.

Detailed Description
-----------------
OBJECTIVES: The primary objective iss to determine the safety of indium (111In) monoclonal antibody (mAb) hu3S193 (111In-hu3S193) given intraperitoneally or intravenously in patients with ovarian carcinoma. Secondary objectives include comparing the localization of 111In-hu3S193 in ovarian cancer tissue after intraperitoneal vs intravenous injection and the biodistribution and pharmacokinetics of this drug when administered intraperitoneally vs intravenously in these patients as well as the formation of human anti-human antibodies (HAHA) in these patients. OUTLINE: Patients are assigned to 1 of 2 treatment arms on a first come sequential basis. Arm I: Patients receive indium (In 111) monoclonal antibody hu3S193 (111In-hu3S193) intraperitoneally over 30 minutes. Arm II: Patients received 111In-hu3S193 intravenously (IV) over 30 minutes. Patients were to undergo surgical debulking 3-7 days following In 111In-hu3S193 administration, and biopsy samples obtained to assess radioactive uptake. Immunohistochemistry was also to be performed. Blood samples were to be obtained to assess serum radioactivity. Whole body imaging was tp be performed 3 hours after infusion of radiolabeled monoclonal antibody, on the day of surgery, and at one time point in between. Patients were followed for 30 days. PROJECTED ACCRUAL: A total of 10 patients (5 per arm) were to be accrued for this study.

Official Title
-----------------
Pilot Trial of Humanized 3S193 Monoclonal Antibody (hu3S193) in Presurgical Patients With Ovarian Cancer

Conditions
-----------------
Ovarian Cancer

Intervention / Treatment
-----------------
* Biological: Monoclonal antibody hu3S193


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Cytologic or pathologic diagnosis consistent with ovarian carcinoma. Scheduled to undergo surgical evaluation. Karnofsky performance status of > 60%. Adequate organ function as defined by: Absolute neutrophil count (ANC) > 1.5 x 10^9/L Platelet count > 100 x 10^9/L Bilirubin < 2.0 mg/dL Aspartate aminotransferase (AST) and Alanine transaminase (ALT) < 2.5 X upper limit of normal Serum creatinine < 2.0 mg/dL Forced expiratory volume at one second (FEV1) and forced vital capacity (FVC)> 70% of predicted Left Ventricular Ejection Fraction >50% Recovered from the toxicity of any prior therapy. No evidence of active infection which requires antibiotic therapy. > 18 years of age. Able to sign written informed consent. Exclusion Criteria Any significant intercurrent medical problems which may limit the amount of antibody they can tolerate, or render them ineligible for surgery. Clinically significant cardiac disease (New York Heart Association Class III/IV, or abnormalities on ECG that are considered by the investigator to place the patient at increased risk), severe debilitating pulmonary disease, active infections or coagulation disorders. Survival expectancy less than 12 weeks. History of autoimmune hepatitis or history of autoimmune disease. Chemotherapy, radiotherapy, or immunotherapy within four weeks prior to receiving hu3S193. Psychiatric, addictive or other disorders that compromise the ability to give informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraperitoneal (IP) Infusion of 111In-hu3S193<br>Hu3S193 was administered intraperitoneally at a dose of 5 mg radiolabeled with 5 millicurie (mCi) of 111In. Patients received 10 mCi 99mTc-sulphur colloid IP administered in 500 ml of normal saline to assure the absence of any loculation or heterogeneous distribution of radioactivity in the peritoneal cavity. A paracentesis catheter was inserted and the hu3S193 was diluted in 100 mL of 5% human serum albumin and administered as a continuous intraperitoneal infusion over 30 minutes. This was followed immediately by 900 mL of normal saline. | Biological: Monoclonal antibody hu3S193<br>* Hu3S193 was to be administered intraperitoneally or intravenously at a dose of 5mg. Doses of hu3S193 were radiolabeled with 5 mCi of 111In.<br>|
| Experimental: Intravenous Infusion of 111In-hu3S193<br>Hu3S193 was to be administered intravenously at a dose of 5 mg radiolabeled with 5 millicurie (mCi) of 111In, diluted in 100 mL of 5% human serum albumin and administered over a 30 minute period. | Biological: Monoclonal antibody hu3S193<br>* Hu3S193 was to be administered intraperitoneally or intravenously at a dose of 5mg. Doses of hu3S193 were radiolabeled with 5 mCi of 111In.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Grade 3 Adverse Events | All toxicities were to be graded according to the Common Toxicity Criteria (CTC) Scale, version 2.0, March 1998.The study was to be terminated upon the occurrence of an adverse event of Grade 3 or greater severity that is considered definitely related to hu3S193. | up to 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ovarian epithelial cancer