Study of the Trifunctional Antibody Catumaxomab to Treat Recurrent Symptomatic Malignant Ascites

A Single-Arm, Open-Label, Phase II Study to Assess the Safety and Efficacy of the Trifunctional Antibody Catumaxomab (Anti-EpCAM x Anti-CD3) Administered Intraperitoneally in Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites

The purpose of this study is to determine whether the investigational drug catumaxomab is a safe and effective treatment for recurrent symptomatic malignant ascites.

A multi-center, phase II study of catumaxomab in ovarian cancer patients with recurrent symptomatic malignant ascites requiring therapeutic paracentesis. Each eligible patient will receive four ascending doses of catumaxomab, administered intraperitoneally via an indwelling catheter. Catumaxomab will be administered as a 3-hour constant rate infusion with a dosing interval of 3-4 days. Each patient will participate in this study for up to 7 months (includes the baseline therapeutic paracentesis and screening period, 11 to 21 days treatment period, and up to 180 days/6 months follow-up), with monthly post-study follow-up for the lifetime of the patient.

Catumaxomab is a trifunctional antibody targeting EpCAM on tumor cells and CD3 on T cells. Trifunctional antibodies represent a new concept for targeted anticancer therapy. This new antibody class has the capability to redirect T cells and accessory cells (e.g. macrophages, dendritic cells (DCs) and natural killer (NK) cells) to the tumor site. According to preclinical data, trifunctional antibodies activate these different immune effector cells, which can trigger a complex anti-tumor immune response.

Inclusion Criteria:

• Signed and dated informed consent
• Histologically confirmed diagnosis of epithelial ovarian cancer, peritoneal cancer, or fallopian tube cancer; any stage at diagnosis [International Federation of Gynecology and Obstetrics (FIGO) Stages I through IV].
• Progression on or ≤ 12 months after primary platinum-based systemic or intraperitoneal (IP) chemotherapy OR relapse following reinduction ≥ 12 months after primary chemotherapy.
• Have refused, failed, or have been deemed not suitable candidates for gemcitabine or liposomal doxorubicin.
• Recurrent symptomatic malignant ascites requiring therapeutic paracentesis
• At least 1 therapeutic paracentesis within 4 weeks prior to baseline paracentesis
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy ≥ 16 weeks
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, and total bilirubin ≤ 1.5 x ULN
• Absolute neutrophil count (ANC) ≥ 1,500/mm3 and platelet count ≥ 75,000/mm3
• Negative serum pregnancy test result at screening in women of childbearing potential (applies to patients without documented menopause or sterility).
• Willingness of patients of childbearing potential to use an effective contraceptive method (i.e., oral contraceptive, cervical cap, diaphragm with spermicide, condom with spermicide, or intrauterine device) during the study and for at least 6 months after the last infusion.

Exclusion Criteria:

• Acute or chronic systemic infection
• Exposure to investigational drugs, chemotherapy or radiotherapy 21 days prior to the first dose of catumaxomab
• Major surgery 2 weeks prior to first dose
• Previous treatment with mouse or rat antibodies
• Known or suspected hypersensitivity to catumaxomab or other monoclonal antibodies
• Body mass index (BMI) < 19 (body weight after paracentesis to be used for calculation of BMI)
• Serum albumin level < 2.0 g/dL
• Reduced nutritional status requiring predominantly parenteral nutrition (> 50% of energy intake). Permanent naso-gastric (NG) feeding tube.
• Ileus in a location that precludes paracentesis
• Extensive liver metastases (> 70% organ volume comprises malignancy)
• Documented brain metastases
• History of myocardial infarction, congestive heart failure or relevant cardiac arrhythmia 3 months prior to the first dose of catumaxomab
• Portal vein obstruction or portal vein thrombosis diagnosed by computed tomography (CT) scan at screening
• Persistent massive pleural effusion or inadequate respiratory function of any other etiology (except if related to ascites symptoms) in the opinion of the investigator
• Any other condition which, according to the investigator, results in an undue risk to the patient by participating in the study
• Prior exposure to catumaxomab