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

This study has been completed.
Sponsor:
Collaborator:
Fresenius Biotech North America
Information provided by (Responsible Party):
Neovii Biotech
ClinicalTrials.gov Identifier:
NCT00326885
First received: May 15, 2006
Last updated: November 14, 2012
Last verified: October 2011
  Purpose

The purpose of this study is to determine whether the investigational drug catumaxomab is a safe and effective treatment for recurrent symptomatic malignant ascites.


Condition Intervention Phase
Malignant Ascites
Drug: catumaxomab
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Neovii Biotech:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 32
Study Start Date: June 2006
Study Completion Date: August 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Catumaxomab 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).

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00326885

Locations
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
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Massachusetts General Hospital
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
Wake-Forest University
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
Sponsors and Collaborators
Neovii Biotech
Fresenius Biotech North America
Investigators
Study Chair: Jonathan Berek, MD MMSc Stanford University Hospital and Clinics, Department of Obstetrics and Gynecology
  More Information

Publications:

Responsible Party: Neovii Biotech
ClinicalTrials.gov Identifier: NCT00326885     History of Changes
Other Study ID Numbers: IP-REM-AC-02-US
Study First Received: May 15, 2006
Results First Received: June 15, 2011
Last Updated: November 14, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Neovii Biotech:
Ascites
Epithelial Cancer
Epithelial Carcinoma
Epithelial Ovarian Cancer
Epithelial Ovarian Carcinoma
Fallopian Tube Cancer
Fallopian Tube Carcinoma
Malignant Ascites
Ovarian Cancer
Ovarian Carcinoma
Ovarian Epithelial Cancer
Ovarian Epithelial Carcinoma
Peritoneal Cancer
Peritoneal Carcinoma
Recurrent Ascites
Recurrent Malignant Ascites
Recurrent Symptomatic Malignant Ascites
Symptomatic Malignant Ascites
Symptomatic Ascites
Malignant ascites
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms

Additional relevant MeSH terms:
Ascites
Pathologic Processes
Antibodies, Bispecific
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 24, 2014