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

September 18, 2018 updated by: Neovii Biotech

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States
        • University of Arizona Cancer Center
    • California
      • La Jolla, California, United States
        • University of San Diego
      • Stanford, California, United States
        • Stanford University Hospital and Clinics
    • Florida
      • Miami, Florida, United States
        • University of Miami
      • Orlando, Florida, United States
        • Florida Hospital Cancer Center
    • Indiana
      • South Bend, Indiana, United States
        • Northern Indiana Cancer Research Consortium
    • Kentucky
      • Louisville, Kentucky, United States
        • University of Louisville Cancer Center
    • Maryland
      • Baltimore, Maryland, United States
        • Johns Hopkins Medical Institute
    • Massachusetts
      • Boston, Massachusetts, United States
        • Dana Farber Cancer Institute
      • Boston, Massachusetts, United States
        • Massachusetts General Hospital
    • Michigan
      • Detroit, Michigan, United States
        • Wayne State University
    • New Hampshire
      • Lebanon, New Hampshire, United States
        • Dartmouth-Hitchock Medical Center
    • New York
      • New York, New York, United States
        • Columbia University Cancer center
    • North Carolina
      • Winston-Salem, North Carolina, United States
        • Wake-Forest University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
        • University of Oklahoma Health Science Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States
        • Magee Women's Hospital, University of Pittsburgh
    • Texas
      • Houston, Texas, United States
        • The Methodist Hospital
    • Utah
      • Salt Lake City, Utah, United States
        • Huntsman Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months
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.
180 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
≥6 months
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.
≥ 6 months
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.
6 months
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.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Neovii Biotech

Collaborators

Fresenius Biotech North America

Investigators

  • Study Chair: Jonathan Berek, MD MMSc, Stanford University Hospital and Clinics, Department of Obstetrics and Gynecology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

May 15, 2006

First Submitted That Met QC Criteria

May 15, 2006

First Posted (Estimate)

May 17, 2006

Study Record Updates

Last Update Posted (Actual)

October 17, 2018

Last Update Submitted That Met QC Criteria

September 18, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IP-REM-AC-02-US

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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