Study of the Trifunctional Antibody Catumaxomab to Treat Recurrent Symptomatic Malignant Ascites
- Registration Number
- NCT00326885
- Lead Sponsor
- Neovii Biotech
- Brief Summary
The purpose of this study is to determine whether the investigational drug catumaxomab is a safe and effective treatment for recurrent symptomatic malignant ascites.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 32
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Catumaxomab catumaxomab -
- Primary Outcome Measures
Name Time Method Increase of Paracentesis/Puncture-free Interval (Ratio) 180 days The parameter to be tested is the ratio of the post-treatment puncture/paracentesis-free interval divided by the pre-treatment puncture/paracentesis-free interval. The pre-treatment interval is defined as the length of time between the patient's most recent paracentesis (baseline) and the subsequent paracentesis necessitated by her increasing ascites-related symptoms. The post-treatment interval is defined as the time between the last dose of catumaxomab plus 1 day to the time of recurrence of ascites requiring therapeutic paracentesis or death, whichever occurred sooner.
The Proportion of Patients Who Achieved at Least a 4-fold Increase of Puncture/Paracentesis-free Interval Following Catumaxomab Relative to Their Pre-treatment Interval. 6 months The parameter to be estimated is the proportion of patients who achieve at least a 4-fold increase in their puncture/paracentesis-free interval. The pretreatment interval is defined as the length of time between the patient's most recent paracentesis (baseline) and the subsequent paracentesis necessitated by her increasing ascites-related symptoms. The post-treatment interval is defined as the time between the last dose of catumaxomab plus 1 day to the time of recurrence of ascites requiring therapeutic paracentesis or death, whichever occurred sooner.
- Secondary Outcome Measures
Name Time Method Puncture/Paracentesis-free Survival (PuFS) ≥6 months Puncture/Paracentesis-free Survival (PuFS), Defined as the Number of Days Between the Date of Last Dose and the Date of Documented End of Study (EoS) Paracentesis or Death, Whichever Occurred First
Overall Survival (OS) ≥ 6 months Overall survival is defined as the interval from the date of first dose to the date of death.
Ascites Signs and Symptoms 6 months Patient-reported ascites symptoms were to be assessed using the patient questionnaire, Functional Assessment of Chronic Illness Therapy - Ascites Index (FACIT-AI). At 6 months following catumaxomab administration, the patient was requested to assess the severity of the following parameters during the past week using a 5-point scale with scores from "0 = not at all" to "4 = very much": anorexia, insomnia, decreased mobility, dyspnea, nausea, vomiting, abdominal pain, abdominal distention, fatigue, early satiety, urinary frequency, constipation, and emotional distress. For the parameters anorexia, insomnia, and decreased mobility, high scores mean good response, for the other parameters low scores mean good response.
Ascites Volume 6 months Ascites volume measurement were to be performed at screening (= prior to baseline), at baseline (= before start of therapy with catumaxomab) and during the 6-month follow-up period when the patient had recurrence of symptomatic ascites requiring therapeutic paracentesis. At each paracentesis, drainage to dryness was to be achieved and the exact volume was to be measured and documented.
Trial Locations
- Locations (18)
Magee Women's Hospital, University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
The Methodist Hospital
🇺🇸Houston, Texas, United States
University of Louisville Cancer Center
🇺🇸Louisville, Kentucky, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Stanford University Hospital and Clinics
🇺🇸Stanford, California, United States
Dartmouth-Hitchock Medical Center
🇺🇸Lebanon, New Hampshire, United States
University of Oklahoma Health Science Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
University of San Diego
🇺🇸La Jolla, California, United States
Northern Indiana Cancer Research Consortium
🇺🇸South Bend, Indiana, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Johns Hopkins Medical Institute
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Wake-Forest University
🇺🇸Winston-Salem, North Carolina, United States
Columbia University Cancer center
🇺🇸New York, New York, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Florida Hospital Cancer Center
🇺🇸Orlando, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States