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

• Sponsor: Neovii Biotech (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00326885
• Collaborator: Fresenius Biotech North America (Industry)
• Enrollment: 32
• Locations: 18
• Arm: 1
• Duration (Months): 50
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Ascites	Drug: catumaxomab	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

1. 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. [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.

2. Increase of Paracentesis/Puncture-free Interval (Ratio) [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.

Secondary Outcome Measures

1. Puncture/Paracentesis-free Survival (PuFS) [≥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

2. Overall Survival (OS) [≥ 6 months]

   Overall survival is defined as the interval from the date of first dose to the date of death.

3. Ascites Signs and Symptoms [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.

4. Ascites Volume [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States
2	University of San Diego	La Jolla	California	United States
3	Stanford University Hospital and Clinics	Stanford	California	United States
4	University of Miami	Miami	Florida	United States
5	Florida Hospital Cancer Center	Orlando	Florida	United States
6	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States
7	University of Louisville Cancer Center	Louisville	Kentucky	United States
8	Johns Hopkins Medical Institute	Baltimore	Maryland	United States
9	Dana Farber Cancer Institute	Boston	Massachusetts	United States
10	Massachusetts General Hospital	Boston	Massachusetts	United States
11	Wayne State University	Detroit	Michigan	United States
12	Dartmouth-Hitchock Medical Center	Lebanon	New Hampshire	United States
13	Columbia University Cancer center	New York	New York	United States
14	Wake-Forest University	Winston-Salem	North Carolina	United States
15	University of Oklahoma Health Science Center	Oklahoma City	Oklahoma	United States
16	Magee Women's Hospital, University of Pittsburgh	Pittsburgh	Pennsylvania	United States
17	The Methodist Hospital	Houston	Texas	United States
18	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

Study Documents (Full-Text)

None provided.

More Information

Publications

• Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO, Ivanchenko VV, Dudnichenko AS, Aleknaviciene B, Razbadauskas A, Gore M, Ganea-Motan E, Ciuleanu T, Wimberger P, Schmittel A, Schmalfeldt B, Burges A, Bokemeyer C, Lindhofer H, Lahr A, Parsons SL. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial. Int J Cancer. 2010 Nov 1;127(9):2209-21. doi: 10.1002/ijc.25423.
• Heiss MM, Ströhlein MA, Jäger M, Kimmig R, Burges A, Schoberth A, Jauch KW, Schildberg FW, Lindhofer H. Immunotherapy of malignant ascites with trifunctional antibodies. Int J Cancer. 2005 Nov 10;117(3):435-43.
• Riesenberg R, Buchner A, Pohla H, Lindhofer H. Lysis of prostate carcinoma cells by trifunctional bispecific antibodies (alpha EpCAM x alpha CD3). J Histochem Cytochem. 2001 Jul;49(7):911-7.
• Ruf P, Kluge M, Jäger M, Burges A, Volovat C, Heiss MM, Hess J, Wimberger P, Brandt B, Lindhofer H. Pharmacokinetics, immunogenicity and bioactivity of the therapeutic antibody catumaxomab intraperitoneally administered to cancer patients. Br J Clin Pharmacol. 2010 Jun;69(6):617-25. doi: 10.1111/j.1365-2125.2010.03635.x.
• Ruf P, Lindhofer H. Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody. Blood. 2001 Oct 15;98(8):2526-34.
• Zeidler R, Mysliwietz J, Csánady M, Walz A, Ziegler I, Schmitt B, Wollenberg B, Lindhofer H. The Fc-region of a new class of intact bispecific antibody mediates activation of accessory cells and NK cells and induces direct phagocytosis of tumour cells. Br J Cancer. 2000 Jul;83(2):261-6.
• Zeidler R, Reisbach G, Wollenberg B, Lang S, Chaubal S, Schmitt B, Lindhofer H. Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing. J Immunol. 1999 Aug 1;163(3):1246-52.

• Responsible Party: Neovii Biotech
• ClinicalTrials.gov Identifier: NCT00326885
• Other Study ID Numbers: IP-REM-AC-02-US
• First Posted: May 17, 2006
• Last Update Posted: Oct 17, 2018
• Last Verified: Sep 1, 2018

• 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; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms
• Additional relevant MeSH terms: Ascites; Catumaxomab

Study Results

Participant Flow

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 Detail	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
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

Baseline Characteristics

Arm/Group Title	Catumaxomab
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 Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	18 56.3%
>=65 years	14 43.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.3 (10.84)
Sex: Female, Male (Count of Participants)
Female	32 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	32 100%

Outcome Measures

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.
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Catumaxomab
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)
Measure Participants	31
Number [proportion of patients]	0.226

2. Secondary Outcome

Title	Puncture/Paracentesis-free Survival (PuFS)
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

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) Per protocol (PP)

Arm/Group Title	Catumaxomab
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)
Measure Participants	32
Median (Full Range) [weeks]	4.2

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined as the interval from the date of first dose to the date of death.
Time Frame	≥ 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Catumaxomab
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)
Measure Participants	32
Median (95% Confidence Interval) [months]	3.6

4. Secondary Outcome

Title	Ascites Signs and Symptoms
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Catumaxomab
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)
Measure Participants	4
I have good appetite	1.5
I am sleeping well	1.0
I am able to get around by myself	1.0
I have been short of breath	1.0
I have nausea	0.5
I have been vomiting	0.5
I have pain in my stomach area	1.0
I have swelling in my stomach area	1.0
I have lack of energy	2.0
When I eat, I seem to get full quickly	2.0
I urinate more frequently	0.0
I am bothered by constipation	1.0
I have been emotionally distressed	0

5. Secondary Outcome

Title	Ascites Volume
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Catumaxomab
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)
Measure Participants	32
prior to baseline (at screening)	2800
baseline (start of therapy)	2050
at puncture visit/ end of study (day 180)	1500

6. Primary Outcome

Title	Increase of Paracentesis/Puncture-free Interval (Ratio)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Full Analysis Set
Arm/Group Description
Measure Participants	31
Median (Full Range) [fold]	2

Adverse Events

Time Frame	6 months
Arm/Group Title	Catumaxomab
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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Catumaxomab
	Affected / at Risk (%)	# Events
Total	24/32 (75%)
Gastrointestinal disorders
Vomiting	6/32 (18.8%)	7
Nausea	5/32 (15.6%)	7
Small intestinal obstruction	4/32 (12.5%)	4
Abdominal pain	2/32 (6.3%)	2
Upper gastrointestinal haemorrhage	2/32 (6.3%)	2
Constipation	1/32 (3.1%)	1
Gastrointestinal haemorrhage	1/32 (3.1%)	1
Large intestinal obstruction	1/32 (3.1%)	1
Oesophagitis	1/32 (3.1%)	1
Peritonitis	1/32 (3.1%)	1
General disorders
Extravasation	2/32 (6.3%)	2
Pyrexia	2/32 (6.3%)	2
Chills	1/32 (3.1%)	1
Device leakage	1/32 (3.1%)	1
Injection site reaction	1/32 (3.1%)	1
Hepatobiliary disorders
Hepatic function abnormal	1/32 (3.1%)	1
Hyperbilirubinaemia	1/32 (3.1%)	1
Infections and infestations
Abdominal abscess	1/32 (3.1%)	1
Bacteraemia	1/32 (3.1%)	2
Sepsis syndrome	1/32 (3.1%)	1
Septic shock	1/32 (3.1%)	1
Metabolism and nutrition disorders
Dehydration	3/32 (9.4%)	3
Hyponatraemia	1/32 (3.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	7/32 (21.9%)	7
Respiratory, thoracic and mediastinal disorders
Pleural effusion	3/32 (9.4%)	3
Pulmonary embolism	3/32 (9.4%)	3
Hypoxia	2/32 (6.3%)	2
Pneumonia aspiration	1/32 (3.1%)	1
Skin and subcutaneous tissue disorders
Rash	1/32 (3.1%)	1
Rash macular	1/32 (3.1%)	1
Vascular disorders
Hypotension	1/32 (3.1%)	1
Other (Not Including Serious) Adverse Events
	Catumaxomab
	Affected / at Risk (%)	# Events
Total	32/32 (100%)
Blood and lymphatic system disorders
Anaemia	10/32 (31.3%)	10
Cardiac disorders
Tachycardia	5/32 (15.6%)	6
Sinus tachycardia	2/32 (6.3%)	2
Eye disorders
Diplopia	2/32 (6.3%)	2
Gastrointestinal disorders
Nausea	24/32 (75%)	39
Vomiting	24/32 (75%)	37
Abdominal pain	16/32 (50%)	19
Constipation	14/32 (43.8%)	15
Diarrhoea	9/32 (28.1%)	11
Abdominal distension	5/32 (15.6%)	6
Small intestinal obstruction	5/32 (15.6%)	5
Abdominal discomfort	3/32 (9.4%)	5
Dyspepsia	3/32 (9.4%)	3
Gastrooesophageal reflux disease	3/32 (9.4%)	3
Abdominal pain upper	2/32 (6.3%)	2
Flatulence	2/32 (6.3%)	2
Upper gastrointestinal haemorrhage	2/32 (6.3%)	2
General disorders
Fatigue	19/32 (59.4%)	21
Pyrexia	19/32 (59.4%)	34
Chills	14/32 (43.8%)	22
Oedema peripheral	9/32 (28.1%)	12
Asthenia	6/32 (18.8%)	6
Catheter site pain	5/32 (15.6%)	6
Oedema	4/32 (12.5%)	5
Performance status decreased	3/32 (9.4%)	3
Catheter site erythema	2/32 (6.3%)	2
Chest pain	2/32 (6.3%)	2
Device leakage	2/32 (6.3%)	2
Extravasation	2/32 (6.3%)	2
Infections and infestations
Candidiasis	3/32 (9.4%)	3
Urinary tract infection	3/32 (9.4%)	3
Pneumonia	2/32 (6.3%)	2
Investigations
Blood alkaline phosphatase increased	4/32 (12.5%)	4
Haemoglobin decreased	4/32 (12.5%)	5
Weight decreased	4/32 (12.5%)	4
Alanine aminotransferase increased	3/32 (9.4%)	3
Aspartate aminotransferase increased	3/32 (9.4%)	3
C-reactive protein increased	3/32 (9.4%)	3
Haematocrit decreased	3/32 (9.4%)	4
Protein total decreased	3/32 (9.4%)	3
Blood albumin decreased	2/32 (6.3%)	2
Blood chloride decreased	2/32 (6.3%)	2
Blood magnesium decreased	2/32 (6.3%)	2
Coagulation time prolonged	2/32 (6.3%)	2
Oxygen saturation decreased	2/32 (6.3%)	2
Urine output decreased	2/32 (6.3%)	2
White blood cell count increased	2/32 (6.3%)	2
Metabolism and nutrition disorders
Decreased appetite	11/32 (34.4%)	13
Dehydration	10/32 (31.3%)	11
Hyponatraemia	7/32 (21.9%)	7
Hypoalbuminaemia	6/32 (18.8%)	6
Hypokalaemia	4/32 (12.5%)	4
Hyperglycaemia	2/32 (6.3%)	2
Polydipsia	2/32 (6.3%)	2
Fluid overload	2/32 (6.3%)	2
Musculoskeletal and connective tissue disorders
Back pain	6/32 (18.8%)	7
Pain in extremity	3/32 (9.4%)	3
Arthralgia	2/32 (6.3%)	3
Muscle spasms	2/32 (6.3%)	2
Myalgia	2/32 (6.3%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	8/32 (25%)	8
Nervous system disorders
Dizziness	4/32 (12.5%)	4
Headache	3/32 (9.4%)	6
Tremor	2/32 (6.3%)	2
Psychiatric disorders
Anxiety	5/32 (15.6%)	5
Confusional state	3/32 (9.4%)	3
Depression	3/32 (9.4%)	3
Insomnia	3/32 (9.4%)	3
Renal and urinary disorders
Proteinuria	3/32 (9.4%)	3
Haematuria	2/32 (6.3%)	3
Renal failure	2/32 (6.3%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnoea	9/32 (28.1%)	10
Cough	8/32 (25%)	8
Pleural effusion	4/32 (12.5%)	4
Pulmonary embolism	3/32 (9.4%)	3
Pulmonary oedema	3/32 (9.4%)	3
Dyspnoea exertional	2/32 (6.3%)	2
Hypoxia	2/32 (6.3%)	2
Oropharyngeal pain	2/32 (6.3%)	2
Skin and subcutaneous tissue disorders
Erythema	6/32 (18.8%)	7
Rash	5/32 (15.6%)	5
Dry skin	2/32 (6.3%)	2
Night sweats	2/32 (6.3%)	2
Vascular disorders
Hypotension	4/32 (12.5%)	5
Hypertension	2/32 (6.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.