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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

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Ascites
Intervention Drug: catumaxomab
Enrollment 32
Recruitment Details 40 patients were recruited and 32 patients were treated and evaluable. For analyses, there were 32 patients in the Full Analysis Set (FAS), 14 patients in the Per-Protocol (PP) population, and 32 patients in the Safety population.
Pre-assignment Details Eligible patients must have undergone at least 1 therapeutic paracentesis (the most recent paracentesis) within 4 weeks prior to the baseline paracentesis.
Arm/Group Title Catumaxomab
Hide Arm/Group Description 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 4 days (10 μg, 20 μg, 50 μg, and 150 μg, respectively)
Period Title: Overall Study
Started 32
Completed 25
Not Completed 7
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             3
Physician Decision             1
Hospice withdrew consent             2
Arm/Group Title Catumaxomab
Hide Arm/Group Description 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 4 days (10 μg, 20 μg, 50 μg, and 150 μg, respectively)
Overall Number of Baseline Participants 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
<=18 years
0
   0.0%
Between 18 and 65 years
18
  56.3%
>=65 years
14
  43.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants
60.3  (10.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Female
32
 100.0%
Male
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 32 participants
32
1.Primary Outcome
Title 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.
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Catumaxomab
Hide Arm/Group Description:
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 4 days (10 μg, 20 μg, 50 μg, and 150 μg, respectively)
Overall Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: proportion of patients
0.226
2.Primary Outcome
Title Increase of Paracentesis/Puncture-free Interval (Ratio)
Hide Description 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.
Time Frame 180 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Full Analysis Set
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 31
Median (Full Range)
Unit of Measure: fold
2
(0.15 to 60)
3.Secondary Outcome
Title Puncture/Paracentesis-free Survival (PuFS)
Hide Description 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
Time Frame ≥6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) Per protocol (PP)
Arm/Group Title Catumaxomab
Hide Arm/Group Description:
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 4 days (10 μg, 20 μg, 50 μg, and 150 μg, respectively)
Overall Number of Participants Analyzed 32
Median (Full Range)
Unit of Measure: weeks
4.2
(2.1 to 7.6)
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the interval from the date of first dose to the date of death.
Time Frame ≥ 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Catumaxomab
Hide Arm/Group Description:
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 4 days (10 μg, 20 μg, 50 μg, and 150 μg, respectively)
Overall Number of Participants Analyzed 32
Median (95% Confidence Interval)
Unit of Measure: months
3.6
(2.2 to 4.6)
5.Secondary Outcome
Title Ascites Signs and Symptoms
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Catumaxomab
Hide Arm/Group Description:
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 4 days (10 μg, 20 μg, 50 μg, and 150 μg, respectively)
Overall Number of Participants Analyzed 4
Median (Full Range)
Unit of Measure: units on a scale
I have good appetite
1.5
(1 to 2)
I am sleeping well
1.0
(1 to 2)
I am able to get around by myself
1.0
(0 to 3)
I have been short of breath
1.0
(1 to 1)
I have nausea
0.5
(0 to 2)
I have been vomiting
0.5
(0 to 1)
I have pain in my stomach area
1.0
(1 to 1)
I have swelling in my stomach area
1.0
(0 to 2)
I have lack of energy
2.0
(1 to 3)
When I eat, I seem to get full quickly
2.0
(2 to 3)
I urinate more frequently
0.0
(0.0 to 2.0)
I am bothered by constipation
1.0
(0 to 1)
I have been emotionally distressed
0
(0 to 0)
6.Secondary Outcome
Title Ascites Volume
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Catumaxomab
Hide Arm/Group Description:
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 4 days (10 μg, 20 μg, 50 μg, and 150 μg, respectively)
Overall Number of Participants Analyzed 32
Median (Full Range)
Unit of Measure: mL
prior to baseline (at screening)
2800
(50 to 8675)
baseline (start of therapy)
2050
(60 to 5500)
at puncture visit/ end of study (day 180)
1500
(0 to 3100)
Time Frame 6 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Catumaxomab
Hide Arm/Group Description 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 4 days (10 μg, 20 μg, 50 μg, and 150 μg, respectively)
All-Cause Mortality
Catumaxomab
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Catumaxomab
Affected / at Risk (%) # Events
Total   24/32 (75.00%)    
Gastrointestinal disorders   
Vomiting * 1  6/32 (18.75%)  7
Nausea * 1  5/32 (15.63%)  7
Small intestinal obstruction * 1  4/32 (12.50%)  4
Abdominal pain * 1  2/32 (6.25%)  2
Upper gastrointestinal haemorrhage * 1  2/32 (6.25%)  2
Constipation * 1  1/32 (3.13%)  1
Gastrointestinal haemorrhage * 1  1/32 (3.13%)  1
Large intestinal obstruction * 1  1/32 (3.13%)  1
Oesophagitis * 1  1/32 (3.13%)  1
Peritonitis * 1  1/32 (3.13%)  1
General disorders   
Extravasation * 1  2/32 (6.25%)  2
Pyrexia * 1  2/32 (6.25%)  2
Chills * 1  1/32 (3.13%)  1
Device leakage * 1  1/32 (3.13%)  1
Injection site reaction * 1  1/32 (3.13%)  1
Hepatobiliary disorders   
Hepatic function abnormal * 1  1/32 (3.13%)  1
Hyperbilirubinaemia * 1  1/32 (3.13%)  1
Infections and infestations   
Abdominal abscess * 1  1/32 (3.13%)  1
Bacteraemia * 1  1/32 (3.13%)  2
Sepsis syndrome * 1  1/32 (3.13%)  1
Septic shock * 1  1/32 (3.13%)  1
Metabolism and nutrition disorders   
Dehydration * 1  3/32 (9.38%)  3
Hyponatraemia * 1  1/32 (3.13%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Malignant neoplasm progression * 1  7/32 (21.88%)  7
Respiratory, thoracic and mediastinal disorders   
Pleural effusion * 1  3/32 (9.38%)  3
Pulmonary embolism * 1  3/32 (9.38%)  3
Hypoxia * 1  2/32 (6.25%)  2
Pneumonia aspiration * 1  1/32 (3.13%)  1
Skin and subcutaneous tissue disorders   
Rash * 1  1/32 (3.13%)  1
Rash macular * 1  1/32 (3.13%)  1
Vascular disorders   
Hypotension * 1  1/32 (3.13%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Catumaxomab
Affected / at Risk (%) # Events
Total   32/32 (100.00%)    
Blood and lymphatic system disorders   
Anaemia * 1  10/32 (31.25%)  10
Cardiac disorders   
Tachycardia * 1  5/32 (15.63%)  6
Sinus tachycardia * 1  2/32 (6.25%)  2
Eye disorders   
Diplopia * 1  2/32 (6.25%)  2
Gastrointestinal disorders   
Nausea * 1  24/32 (75.00%)  39
Vomiting * 1  24/32 (75.00%)  37
Abdominal pain * 1  16/32 (50.00%)  19
Constipation * 1  14/32 (43.75%)  15
Diarrhoea * 1  9/32 (28.13%)  11
Abdominal distension * 1  5/32 (15.63%)  6
Small intestinal obstruction * 1  5/32 (15.63%)  5
Abdominal discomfort * 1  3/32 (9.38%)  5
Dyspepsia * 1  3/32 (9.38%)  3
Gastrooesophageal reflux disease * 1  3/32 (9.38%)  3
Abdominal pain upper * 1  2/32 (6.25%)  2
Flatulence * 1  2/32 (6.25%)  2
Upper gastrointestinal haemorrhage * 1  2/32 (6.25%)  2
General disorders   
Fatigue * 1  19/32 (59.38%)  21
Pyrexia * 1  19/32 (59.38%)  34
Chills * 1  14/32 (43.75%)  22
Oedema peripheral * 1  9/32 (28.13%)  12
Asthenia * 1  6/32 (18.75%)  6
Catheter site pain * 1  5/32 (15.63%)  6
Oedema * 1  4/32 (12.50%)  5
Performance status decreased * 1  3/32 (9.38%)  3
Catheter site erythema * 1  2/32 (6.25%)  2
Chest pain * 1  2/32 (6.25%)  2
Device leakage * 1  2/32 (6.25%)  2
Extravasation * 1  2/32 (6.25%)  2
Infections and infestations   
Candidiasis * 1  3/32 (9.38%)  3
Urinary tract infection * 1  3/32 (9.38%)  3
Pneumonia * 1  2/32 (6.25%)  2
Investigations   
Blood alkaline phosphatase increased * 1  4/32 (12.50%)  4
Haemoglobin decreased * 1  4/32 (12.50%)  5
Weight decreased * 1  4/32 (12.50%)  4
Alanine aminotransferase increased * 1  3/32 (9.38%)  3
Aspartate aminotransferase increased * 1  3/32 (9.38%)  3
C-reactive protein increased * 1  3/32 (9.38%)  3
Haematocrit decreased * 1  3/32 (9.38%)  4
Protein total decreased * 1  3/32 (9.38%)  3
Blood albumin decreased * 1  2/32 (6.25%)  2
Blood chloride decreased * 1  2/32 (6.25%)  2
Blood magnesium decreased * 1  2/32 (6.25%)  2
Coagulation time prolonged * 1  2/32 (6.25%)  2
Oxygen saturation decreased * 1  2/32 (6.25%)  2
Urine output decreased * 1  2/32 (6.25%)  2
White blood cell count increased * 1  2/32 (6.25%)  2
Metabolism and nutrition disorders   
Decreased appetite * 1  11/32 (34.38%)  13
Dehydration * 1  10/32 (31.25%)  11
Hyponatraemia * 1  7/32 (21.88%)  7
Hypoalbuminaemia * 1  6/32 (18.75%)  6
Hypokalaemia * 1  4/32 (12.50%)  4
Hyperglycaemia * 1  2/32 (6.25%)  2
Polydipsia * 1  2/32 (6.25%)  2
Fluid overload * 1  2/32 (6.25%)  2
Musculoskeletal and connective tissue disorders   
Back pain * 1  6/32 (18.75%)  7
Pain in extremity * 1  3/32 (9.38%)  3
Arthralgia * 1  2/32 (6.25%)  3
Muscle spasms * 1  2/32 (6.25%)  2
Myalgia * 1  2/32 (6.25%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Malignant neoplasm progression * 1  8/32 (25.00%)  8
Nervous system disorders   
Dizziness * 1  4/32 (12.50%)  4
Headache * 1  3/32 (9.38%)  6
Tremor * 1  2/32 (6.25%)  2
Psychiatric disorders   
Anxiety * 1  5/32 (15.63%)  5
Confusional state * 1  3/32 (9.38%)  3
Depression * 1  3/32 (9.38%)  3
Insomnia * 1  3/32 (9.38%)  3
Renal and urinary disorders   
Proteinuria * 1  3/32 (9.38%)  3
Haematuria * 1  2/32 (6.25%)  3
Renal failure * 1  2/32 (6.25%)  2
Respiratory, thoracic and mediastinal disorders   
Dyspnoea * 1  9/32 (28.13%)  10
Cough * 1  8/32 (25.00%)  8
Pleural effusion * 1  4/32 (12.50%)  4
Pulmonary embolism * 1  3/32 (9.38%)  3
Pulmonary oedema * 1  3/32 (9.38%)  3
Dyspnoea exertional * 1  2/32 (6.25%)  2
Hypoxia * 1  2/32 (6.25%)  2
Oropharyngeal pain * 1  2/32 (6.25%)  2
Skin and subcutaneous tissue disorders   
Erythema * 1  6/32 (18.75%)  7
Rash * 1  5/32 (15.63%)  5
Dry skin * 1  2/32 (6.25%)  2
Night sweats * 1  2/32 (6.25%)  2
Vascular disorders   
Hypotension * 1  4/32 (12.50%)  5
Hypertension * 1  2/32 (6.25%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Site may publish the results of the Study after such cooperative publication, or 1 year after Sponsor's final evaluation of all the Study data from all sites, whichever occurs first. Prior to any submission for publication, presentation, or communication of results or information arising from the Study, Investigator shall provide Fresenius Biotech at least 90 days for review and comment upon the manuscript or other material for such publication or presentation.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Manager, Regulatory Affairs
Organization: Fresenius Biotech
Phone: 781-699-4652
EMail: bao.le@fresenius-biotech.com
Publications:
Layout table for additonal information
Responsible Party: Neovii Biotech
ClinicalTrials.gov Identifier: NCT00326885     History of Changes
Other Study ID Numbers: IP-REM-AC-02-US
First Submitted: May 15, 2006
First Posted: May 17, 2006
Results First Submitted: June 15, 2011
Results First Posted: December 11, 2012
Last Update Posted: October 17, 2018