Study of the Trifunctional Antibody Catumaxomab to Treat 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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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 Proportion of Patients Who Achieved at Least a 4-fold Increase of Puncture/Paracentesis-free Interval Following Catumaxomab Relative to Their Pre-treatment Interval. [ Time Frame: 6 months ] [ Designated as safety issue: No ]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.
- Increase of Paracentesis/Puncture-free Interval (Ratio) [ Time Frame: 180 days ] [ Designated as safety issue: No ]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.
- Puncture/Paracentesis-free Survival (PuFS) [ Time Frame: ≥6 months ] [ Designated as safety issue: No ]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) [ Time Frame: ≥ 6 months ] [ Designated as safety issue: No ]Overall survival is defined as the interval from the date of first dose to the date of death.
- Ascites Signs and Symptoms [ Time Frame: 6 months ] [ Designated as safety issue: No ]Patient-reported ascites symptoms were to be assessed using the patient questionnaire, 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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]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.
|Study Start Date:||June 2006|
|Study Completion Date:||August 2010|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
Catumaxomab is administered intraperitoneally via an indwelling catheter (or port) as a 3-hour infusion 4 times (Days 0, 3, 7, and 10) in ascending doses (10 mcg, 20 mcg, 50 mcg, and 150 mcg, respectively).
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.
|United States, Arizona|
|University of Arizona Cancer Center|
|Tucson, Arizona, United States|
|United States, California|
|University of San Diego|
|La Jolla, California, United States|
|Stanford University Hospital and Clinics|
|Stanford, California, United States|
|United States, Florida|
|University of Miami|
|Miami, Florida, United States|
|Florida Hospital Cancer Center|
|Orlando, Florida, United States|
|United States, Indiana|
|Northern Indiana Cancer Research Consortium|
|South Bend, Indiana, United States|
|United States, Kentucky|
|University of Louisville Cancer Center|
|Louisville, Kentucky, United States|
|United States, Maryland|
|Johns Hopkins Medical Institute|
|Baltimore, Maryland, United States|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States|
|United States, Michigan|
|Wayne State University|
|Detroit, Michigan, United States|
|United States, New Hampshire|
|Dartmouth-Hitchock Medical Center|
|Lebanon, New Hampshire, United States|
|United States, New York|
|Columbia University Cancer center|
|New York, New York, United States|
|United States, North Carolina|
|Winston-Salem, North Carolina, United States|
|United States, Oklahoma|
|University of Oklahoma Health Science Center|
|Oklahoma City, Oklahoma, United States|
|United States, Pennsylvania|
|Magee Women's Hospital, University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States|
|United States, Texas|
|The Methodist Hospital|
|Houston, Texas, United States|
|United States, Utah|
|Huntsman Cancer Institute|
|Salt Lake City, Utah, United States|
|Study Chair:||Jonathan Berek, MD MMSc||Stanford University Hospital and Clinics, Department of Obstetrics and Gynecology|