Safety and Efficacy Study of Catumaxomab to Treat Ovarian Cancer After a Complete Response to Chemotherapy

An Open-Label, Single-Arm, Phase II Safety and Tolerability Study of Catumaxomab (Anti-EpCAM x Anti-CD3) in Women With Advanced Epithelial Ovarian Cancer After a Complete Response to Chemotherapy

The purpose of this study is to determine whether the investigational drug catumaxomab delivered in the planned treatment schedule is a safe and effective treatment for women with advanced ovarian cancer who experience a complete response to chemotherapy.

A multi-center, phase II study of catumaxomab in ovarian cancer patients who experience a complete response to chemotherapy. Each eligible patient will receive four ascending doses of catumaxomab, administered intraperitoneally via an indwelling catheter or port. 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 4 months (includes the baseline screening period, 11 to 21 days treatment period, and up to 90 days/3 months follow-up), with post-study follow-up every 3 months for 2 years.

Catumaxomab is a trifunctional antibody targeting epithelial cell adhesion molecule (EpCAM) on tumor cells and CD3 (cluster of differentiation 3) 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 form before any protocol-specific screening procedures
• Histologically confirmed diagnosis of epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIb - IV
• Optimal or sub-optimal cytoreductive surgery
• Clinical complete response to platinum and taxane-based therapy consisting of at least four cycles, based on computed tomography (CT) scan and a CA-125 (cancer antigen 125) level below 35 U/mL
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Last dose of platinum and taxane-based therapy completed within 6 weeks prior to the start of catumaxomab treatment
• 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 chemotherapy, radiotherapy, immunotherapy or investigational anti-cancer therapy within 6 weeks of first dose of catumaxomab other than last regimen of platinum and taxane chemotherapy as outlined in protocol

• Known human immunodeficiency virus (HIV) infection

• Previous treatment with non-humanized murine (rat or mouse) monoclonal antibodies (mAb)

• Inadequate renal function (creatinine > 1.5 x upper limit of normal [ULN])

• Inadequate hepatic function:

  • Alanine aminotransferase (ALT) > 2.5 x ULN or
  • Aspartate aminotransferase (AST) > 2.5 x ULN or
  • Bilirubin > 1.5 x ULN

• Platelets < 100,000 cells/mm^3

• Absolute neutrophil count (ANC) < 1,500 cells/mm^3

• History of myocardial infarction, congestive heart failure or relevant cardiac arrhythmia within the last 6 months

• No other malignancy within the past 5 years except non-melanoma skin cancer or carcinoma in situ of the cervix if adequately treated

• No history of brain metastases

• Any further condition or disease that would, in the opinion of the Investigator, expose the patient to undue risk