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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00326885
Recruitment Status : Completed
First Posted : May 17, 2006
Results First Posted : December 11, 2012
Last Update Posted : October 17, 2018
Sponsor:
Collaborator:
Fresenius Biotech North America
Information provided by (Responsible Party):
Neovii Biotech

Tracking Information
First Submitted Date  ICMJE May 15, 2006
First Posted Date  ICMJE May 17, 2006
Results First Submitted Date  ICMJE June 15, 2011
Results First Posted Date  ICMJE December 11, 2012
Last Update Posted Date October 17, 2018
Study Start Date  ICMJE June 2006
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2012)
  • 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 ]
    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 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 15, 2006)
paracentesis-free interval post-treatment compared to pre-treatment interval
Change History Complete list of historical versions of study NCT00326885 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2016)
  • Puncture/Paracentesis-free Survival (PuFS) [ Time Frame: ≥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) [ Time Frame: ≥ 6 months ]
    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 ]
    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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2006)
  • clinical benefit by evaluation of ascites-related signs and symptoms
  • safety and tolerability
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Trifunctional Antibody Catumaxomab to Treat Recurrent Symptomatic Malignant Ascites
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Ascites
Intervention  ICMJE Drug: catumaxomab
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).
Study Arms  ICMJE Experimental: Catumaxomab
Intervention: Drug: catumaxomab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 14, 2012)
32
Original Enrollment  ICMJE
 (submitted: May 15, 2006)
35
Actual Study Completion Date  ICMJE August 2010
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00326885
Other Study ID Numbers  ICMJE IP-REM-AC-02-US
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Neovii Biotech
Study Sponsor  ICMJE Neovii Biotech
Collaborators  ICMJE Fresenius Biotech North America
Investigators  ICMJE
Study Chair: Jonathan Berek, MD MMSc Stanford University Hospital and Clinics, Department of Obstetrics and Gynecology
PRS Account Neovii Biotech
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP