Clinical trial NCT00006099: Monoclonal Antibody Therapy in Treating Patients Scheduled for Surgery to Remove Ovarian Cancer
Official title: Pilot Trial of Humanized 3S193 Monoclonal Antibody (hu3S193) in Presurgical Patients With Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Ovarian Cancer
Keywords: ovarian epithelial cancer
Lead sponsor: Ludwig Institute for Cancer Research
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-12-23
Enrollment: 1
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

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.

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.

Primary outcomes:
measure: Number of Subjects With Grade 3 Adverse Events
timeFrame: up to 30 days
Secondary outcomes:
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: Chaitanya R. Divgi, MD
role: STUDY_CHAIR
References: