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

Phase 2

Completed

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
catumaxomab	catumaxomab	-

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Completed a 4-dose Series of Catumaxomab Infusions (Defined as 10-20-50-150 Micrograms) Within 21 Days	21 days

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Negative (Undetectable) Humoral Immune Responses to Catumaxomab Therapy	2 months	Humoral immune response of participants with functional immune system to catumaxomab can provide important information regarding why a therapy may work for some participants and not for others. An undetectable humoral response by itself does not necessarily imply lack of study drug activity. Humoral response is one of the possible selected measurements of the study drug activity at a time point in the study.
Number of Participants With no Residual Disease Prior to Catumaxomab Treatment Via 2nd-look Laparoscopy or Laparotomy (These Procedures Are Optional)	Baseline
Median Time of Progression-free Survival in Weeks (Post-study for 24 Months)	2 years
Number of Participants Who Survived (Post-study at 24 Month Visit)	2 years	Number of participants who survived (post-study at 24 month visit) is the number of participants who did not die
Number of Participants With no Residual Disease at 3 Months After Catumaxomab Treatment Via 3rd-look Laparoscopy or Laparotomy (These Procedures Are Optional)	3 months

Locations (12): University of New Mexico
🇺🇸
Albuquerque, New Mexico, United States
Stanford University of Obstetrics and Gynecology
🇺🇸
Stanford, California, United States
Gynecologic Oncology - Hinsdale
🇺🇸
Hinsdale, Illinois, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
South Carolina Oncology Associates
🇺🇸
Columbia, South Carolina, United States
Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
Magee-Women Hospital of UPMC
🇺🇸
Pittsburg, Pennsylvania, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Dartmouth-Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Florida Hospital Cancer Institute
🇺🇸
Orlando, Florida, United States
Michiana Hematology Oncology P.C.
🇺🇸
South Bend, Indiana, United States
James Graham Brown Cancer Center
🇺🇸
Louisville, Kentucky, United States