Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer

OBJECTIVES:

Primary

• Determine the safety and maximum tolerated dose of intraperitoneally (IP) administered yttrium-90 (90Y) radiolabeled monoclonal antibody (mAB) hu3S193 (90Y-hu3S193) in patients with advanced ovarian epithelial cancer.

Secondary

• Determine the localization and whole body and abdominal clearance of 90Y-hu3S193 using indium-111 (111In) radiolabeled hu3S193 and gamma camera imaging.
• Determine the serum pharmacokinetics of hu3S193 using gamma well counting.
• Determine the antibody response as measured by human anti-human antibody response (HAHA).

OUTLINE: This is a dose-escalation study of the yttrium-90 radiolabeled monoclonal antibody, 90Y-hu3S193.

Patients received technetium (99mTc-sulfur colloid) IP and underwent abdominal imaging on day 1. Provided the distribution of the 99mTC-sulfur colloid was deemed adequate, patients then received 90Y-hu3S193 IP. 111In-hu3S193 was also administered IP over 30 minutes on day 1 to enable gamma camera imaging. Within 3-5 hours after antibody administration, patients underwent whole body imaging and single-photon emission-computed tomography (SPECT) imaging of the abdomen and pelvis.

Cohorts of 3-6 patients were to receive escalating doses of 90Y-hu3S193 until the maximum tolerated dose (MTD) was determined. The MTD was defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients were to be followed every 3 months for at least 2 years and then every 6 months for up to 5 years.

Inclusion criteria

• Histologically confirmed non-mucinous ovarian adenocarcinoma.
• Persistent or recurrent intraperitoneal cancer following platinum/taxane-based therapy for Stage 3 ovarian cancer.
• Patients with residual disease < 2cm will be candidates for this study.
• The following laboratory and clinical results within the last 2 weeks prior to study day 1:

Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; Platelet count ≥ 100 x 10^9/L; Serum bilirubin ≤ 2.0 mg/dL; Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) ≤ 2.5 x ULN; Serum creatinine ≤2.0 mg/dL; Forced expiratory volume (FEV1) ≥60% of predicted; Forced vital capacity (FVC) ≥60% of predicted; Diffusion capacity ≥55% of predicted; Left ventricular ejection fraction (LVEF) ≥50%;

• Karnofsky performance status ≥ 70.
• Before any trial-specific procedures or treatment can be performed, the patient or legally authorized guardian or representative must give witnessed written informed consent for participation in the trial.
• Placement of an intra-abdominal catheter at the time of surgery.

Exclusion criteria

• Active parenchymal disease (i.e., Stage IV International Federation of Gynecology and Obstetrics (FIGO) classification).
• Presence of symptomatic extra abdominal metastases.
• Known central nervous system (CNS) tumor involvement.
• Clinically significant heart disease (New York Heart Association Class III or IV).
• ECG demonstrating clinically significant arrhythmias or evidence of prior myocardial infarction.
• Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders that may limit the amount of antibody they can tolerate or render them ineligible for surgery.
• Chronic inflammatory bowel disease.
• Chemotherapy, biologic therapy, or immunotherapy within 4 weeks prior to enrollment.
• Pregnancy or lactation.
• Patients who are positive for human anti-human antibodies (HAHA) and/or who have received a murine monoclonal antibody.