Open-label, Randomized, Multicenter, Phase IV Trial Comparing Parenteral Nutrition Using Eurotubes® vs. Traditional 2/3-chamber Bags in Subjects With Metastatic or Localized Solid Tumors Requiring Parenteral Nutrition - The PEKANNUSS Trial
Conditions: Solid Tumor
Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

 
 
 
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PEKANNUSS 
Open-label, randomized, multicenter, phase IV trial comparing 
parenteral nutrition using Eurotubes® vs. traditional 2/3-chamber 
bags in subjects with metastatic or localized solid tumors 
requiring parenteral nutrition 
 – The PEKANNUSS Trial 
 
 
ClinicalTrials.gov ID:  
NCT04105777 
Sponsor’s Protocol Code:  PEKANNUSS 
AIO Study Number: 
AIO-LQ-0119/ass 
 
Lead Coordinating Investigator (LKP) 
Prof. Dr. med. Thorsten Oliver Götze 
Krankenhaus Nordwest 
Steinbacher Hohl 2-26 
60488 Frankfurt am Main 
 
 
 
 
Steering Committee 
Dr. med. Jann Arends,  
Freiburg 
 
Prof. Dr. med. Thorsten Oliver Götze, 
Frankfurt am Main 
PD Dr. med. Georg Martin Haag, 
Heidelberg 
Prof. Dr. med. Ralf-Dieter Hofheinz, 
Mannheim 
Dipl. oec. troph. Ingeborg Rötzer, 
Frankfurt am Main 
Prof. Dr. med. Hubert Serve,  
Frankfurt am Main 
Deputy Lead Coordinating Investigators 
Dr. med. Georg Martin Haag 
Nationales Centrum für Tumorerkrankungen (NCT) 
Universitätsklinikum Heidelberg 
Im Neuenheimer Feld 460 
69120 Heidelberg 
 
 
Prof. Dr. med. Ralf-Dieter Hofheinz 
Universitätsmedizin Mannheim  
Theodor-Kutzer-Ufer 1-3 
68167 Mannheim 
 
 
 
Sponsor Representative 
Prof. Dr. med. Salah-Eddin Al-Batran 
Institut für Klinische Krebsforschung IKF GmbH 
at Krankenhaus Nordwest 
Steinbacher Hohl 2-26 
60488 Frankfurt am Main 
 
Sponsor 
Institut für Klinische Krebsforschung IKF GmbH 
at Krankenhaus Nordwest 
Steinbacher Hohl 2-26 
60488 Frankfurt am Main 
Statistics and Data 
Institut für Klinische Krebsforschung IKF GmbH 
at Krankenhaus Nordwest  
Steinbacher Hohl 2-26 
60488 Frankfurt am Main 

 
 
 
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Study Statistician  
M.Sc. Marina Schaaf 
Institut für Klinische Krebsforschung IKF GmbH 
at Krankenhaus Nordwest 
Steinbacher Hohl 2-26 
60488 Frankfurt am Main 
 
 
Independent Data Monitoring Committee 
Dr. Axel Hinke, 
Düsseldorf 
Prof. Dr. med. Dr. phil. Fuat Oduncu, 
München 
Prof. Dr. med. G.-Andre Banat, 
Bad Nauheim 
 
Institutional Review Board (Ethics 
Committee) 
Ethik-Kommission  
bei der Landesärztekammer Hessen 
Im Vogelsgesang 3 
60488 Frankfurt am Main 
 
Nutritional Consultant 
Dipl. oec. troph. Ingeborg Rötzer 
Nationales Centrum für Tumorerkrankungen (NCT) 
Universitätsklinikum Heidelberg 
Im Neuenheimer Feld 460 
69120 Heidelberg 
 
Clinical Trial Management 
Institut für Klinische Krebsforschung IKF GmbH 
at Krankenhaus Nordwest  
Steinbacher Hohl 2-26 
60488 Frankfurt am Main 
Germany  
 
 
 
 
 
 
CONFIDENTIALITY STATEMENT 
This document is the confidential property of Institut für Klinische Krebsforschung IKF GmbH at 
Krankenhaus Nordwest. No part of it may be transmitted, reproduced, published, or used by other 
persons without the permission of Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus 
Nordwest. 
 
 

 
 
 
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Signatures 
 
 
Lead Coordinating Investigator (LKP)  
Prof. Dr. med. Thorsten Oliver Götze 
 
_______________________________  
______________________________________ 
Place and date  
 
 
 
Signature 
 
 
Sponsor Representative 
Prof. Dr. med. Salah-Eddin Al-Batran 
 
_______________________________  
______________________________________ 
Place and date  
 
 
 
Signature 
 
 
 
 
Site / Principal Investigator  
 
Site: _____________________________ 
Site-No.: __________  
 
Principal Investigator (Print name): _____________________________ 
I have read and checked the protocol diligently; I comply with the stated demands and requirements 
and agree to conduct the study according to the applicable guidelines of Good Clinical Practice (GCP) 
and the requirements of the responsible authorities in regard to reconciliation of original data and to 
audits/inspections.  
I consent to the safety reporting obligations as indicated in the respective protocol section below.  
 
_______________________________  
______________________________________ 
Place and Date  
 
 
 
Signature Principal Investigator 
 
 
 

 
 
 
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1 Table of contents 
1 
Table of contents .............................................................................................................................. 4 
2 
Relevant Abbreviations .................................................................................................................... 6 
3 
Background and rationale ................................................................................................................ 7 
3.1 
The medical problem ................................................................................................................7 
3.2 
Background and Rationale .......................................................................................................8 
3.3 
Parenteral nutrition .................................................................................................................10 
3.3.1 
Traditional 2/3-chamber bags ........................................................................................ 10 
3.3.2 
Pharmacy-compounding ................................................................................................ 11 
3.3.3 
Eurotubes® ..................................................................................................................... 11 
3.4 
Studies on parenteral nutrition and infection ..........................................................................11 
3.5 
Rationale for PEKANNUSS trial ...........................................................................................12 
3.6 
The relevance of this study to current care and benefit-risk assessment ................................13 
4 
Study design ................................................................................................................................... 14 
5 
Objectives and Endpoints ............................................................................................................... 17 
5.1 
Objectives ...............................................................................................................................17 
5.1.1 
Primary objective........................................................................................................... 17 
5.1.2 
Secondary Objectives .................................................................................................... 17 
5.2 
Endpoints ................................................................................................................................17 
5.2.1 
Primary endpoint ........................................................................................................... 17 
5.2.2 
Secondary endpoints ...................................................................................................... 18 
6 
Statistical design ............................................................................................................................ 19 
6.1 
Sample size calculation ..........................................................................................................19 
6.2 
Study Duration .......................................................................................................................19 
6.3 
Analysis ..................................................................................................................................20 
6.3.1 
Study populations for the analysis ................................................................................. 20 
6.3.2 
Statistical methods for the analysis ............................................................................... 21 
7 
Patient Selection ............................................................................................................................. 22 
7.1 
Inclusion Criteria ....................................................................................................................22 
7.2 
Exclusion Criteria ...................................................................................................................23 
8 
Therapy scheme ............................................................................................................................. 23 
9 
Treatment schedule and schedule of assessments .......................................................................... 29 
9.1 
Schedule of assessments .........................................................................................................30 
10 References ...................................................................................................................................... 32 
 
 

 
 
 
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List of tables 
Table 1: Schedule of Assessments ........................................................................................................ 30 
Table 2: ECOG Performance Status as developed by the Eastern Cooperative Oncology Group Fehler! 
Textmarke nicht definiert. 
 
List of figures 
Figure 1: Study Scheme. ....................................................................................................................... 15 
Figure 2: Recruitment, Randomization and Treatment setting. ....... Fehler! Textmarke nicht definiert. 
Figure 3: Schematic overview of Eurotubes®. ................................. Fehler! Textmarke nicht definiert. 
Figure 4: Treatment schedule and schedule of assessments. ................................................................. 29 
 
 

 
 
 
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2 Relevant Abbreviations 
ADE  
Adverse Device Effect 
AE 
 
Adverse Event 
ALT  
Alanine transaminase 
AST   
Aspartate transaminase 
BfArM 
Bundesinstitut für Arzneimittel 
 
 
und Medizinprodukte 
BMI 
 
Body Mass Index 
BSI 
 
Bloodstream infections 
CC  
 
Cancer anorexia-cachexia  
CLABSI  
Central line-associated  
 
 
bloodstream infections 
COM  
Compounded bag 
CRBSI 
Catheter related  
 
 
 
bloodstream infection 
CRP 
 
C-reactive protein 
CRI 
 
Catheter Related Infection 
CTC  
Common toxicity criteria 
ECOG  
Eastern Cooperative Oncology 
 
 
Group 
EDC  
Electronic data capture 
EOT  
End of treatment 
(e)CRF 
(electronic) case report form 
ESPEN 
European Society of Parenteral 
 
 
and Enteral Nutrition 
GCP  
Good Clinical Practice 
GMP   
Good Manufacturing Practice  
GOT  
Glutamic oxaloacetic  
 
 
transaminase 
GPT 
 
Glutamate-pyruvate   
 
 
transaminase 
HPN  
Home parenteral nutrition 
HPN-PROQ Home parenteral nutrition  
 
 
Patient-reported outcome  
 
 
Questionnaire 
ICH 
 
International Council for  
 
 
Harmonisation 
IDMC   
Independent Data Monitoring 
 
 
Committee 
IIT 
 
Investigator-initiated trial 
IRB 
 
Institutional Review Board 
ISF 
 
Investigator site file 
ITT 
 
Intent-to-treat 
IWRS  
Interactive Web Response  
 
 
Systems 
LDH  
Lactate dehydrogenase 
 
 
LKP 
 
Leiter der Klinischen  
 
 
Prüfung/Lead Coordinating 
 
 
Investigator 
MCB  
Multi-chamber bags 
mGPS  
modified Glasgow  
 
 
Prognostic Score 
MPG  
Medizinproduktegesetz 
NI 
 
Nutritional intervention 
NRS  
Nutritional Risk Screening 
OS 
 
Overall survival  
PN  
 
Parenteral nutrition  
PP 
 
Per protocol 
QoL   
Quality of life 
SAP 
 
Statistical analysis plan 
SAS 
 
Statistical Analysis System 
SmPC  
Summary of Product  
 
 
Characteristics 
WHO  
World Health Organization 
 

 
 
 
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To avoid misunderstandings, the following terms shall be clarified: In the context of this 
study, the term “standard PN” refers to the standard composition of the PN. The 2/3-chamber 
bags, that have been used in clinical routine for decades (industrially manufactured bags as 
well as pharmacy-compounded bags) will be referred to as “traditional” bags, that will be 
tested vs. Eurotubes®.  
3 Background and rationale 
3.1 
The medical problem 
Cancer is often characterized by extensive invasion, early metastases, and, in many cases, a 
rapidly occurring marked cachexia leading to a very limited prognosis especially in the 
metastatic situation. 
Cachexia is a strong and independent predictor of mortality, poor therapeutic response, 
diminished functional capacity, and reduced quality of life (QoL). It is defined as the 
debilitating state of involuntary weight loss, often connected with anorexia, tissue wasting, 
malnutrition, and inability for natural nutrition intake. The combination of these symptoms, 
also characterized by systemic inflammation, is also named „cancer anorexia-cachexia 
syndrome" (CC) [Vanhoutte et al., 2016; Fearon et. al, 2011]. The most important phenotypic 
feature is muscle wasting and functional impairment as a result of increased protein degradation 
and reduced protein synthesis or both [Bossola et al., 2007]. The syndrome is life-threatening 
and debilitating for approximately 50% of all cancer subjects [Bossola et al., 2007]. 
As reported, the QoL is significantly impaired in CC subjects and there is evidence for increased 
morbidity and mortality of subjects with CC [Bossola et al., 2007]. Subjects suffering from CC 
commonly have derangements in basal metabolic rate as well as reduced appetite and food 
intake. Even moderate weight loss is associated with psychological stress and lower QoL. 
Furthermore, CC affects subject’s response to chemotherapy [Bossola et al., 2007]. 
Malnourished patients are more difficult to guide through chemotherapy experiencing more 
severe side effects resulting in progressive cachexia. The outcomes of subjects with CC 
receiving chemotherapy can be improved with nutritional intervention (NI) [Bauer and Capra, 
2005]. Supplementation with parenteral nutrition (PN) improves the QoL in subjects with 
advanced CC. There is also data indicating that NI has a synergistic effect with anti-cancer 

 
 
 
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therapy and results in better clinical outcome [Ravasco et al., 2005a; Ravasco et al., 2005b; 
Bauer and Capra, 2005; Caccialanza R. et al., 2018].  
The European Society of Parenteral and Enteral Nutrition (ESPEN) recommends PN only for 
malnourished subjects but does not reflect the situation in CC patients. Nevertheless, PN has 
become a standard of care in cancer patients who are not able to maintain their weight or who 
are at risk of suffering cachexia. PN is now widely accepted as an important component of 
cancer patients’ treatment in the oncology community and is covered by the patients’ 
insurances. 
Despite recent advances in PN for cancer, several clinical problems are still unresolved: 
1. Patients receiving PN are dependent on home nursing service, which represent a major 
limitation of their autonomy and quality of life. 
2. Patients receiving PN are at high risk of developing blood stream infections. 
3. The potential benefit of reduced glucose levels and in the consequence higher levels of 
fat is a long-lasting question that has not been evaluated yet. 
3.2 
Background and Rationale 
Approximately 50% of all cancer subjects suffer from CC and its severe impact on QoL and 
response to chemotherapy [Bossola et al., 2007]. Especially in the advanced stages, it cannot 
be fully cured by increased food intake or oral supplements and requires supportive or total 
parenteral nutrition. If needed, patients can live on PN for an unlimited time, the mean 
administration period varies depending on the underlying disease and the patient’s general 
condition. However, the change from oral food intake to PN is associated with many changes 
in the subject’s everyday life that lead to restriction of autonomy and flexibility. CC patients 
are often unable to handle the connection and disconnection of the nutrition bags to their 
catheter correctly on their own, especially when supplements need to be added. Nursing services 
need to visit the subject daily to perform the PN administration. The infusion takes around 12 
to 14 hours to finish and is typically administered in the evening to be infused overnight. The 
subjects’ daily life is highly determined by the appointments of the nursing service, overnight 
stays away from home are nearly impossible and the dependency on outside assistance can 
diminish the patients’ self-esteem and QoL. The extent to which these limitations to the 
subject’s self-determination impact the QoL is currently poorly studied and needs further 

 
 
 
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investigation. Subsequently, it is of high interest to assess if the QoL shows to be higher in 
subjects performing the PN administration autonomously without nursing service assistance. 
Furthermore, data has shown that PN is accompanied by an increased risk of blood stream 
infections (BSI) [Dissanaike et al., 2007] and is an independent risk factor for both catheter-
related bloodstream infections (CRBSI) and central line-associated bloodstream infections 
(CLABSI) [Beghetto et al., 2005]. BSI represent 15% of all nosocomial infections and are 
associated with increased mortality and other serious medical conditions such as severe sepsis 
or septic shock [Pontes-Arruda et al., 2012]. In addition to the safety aspect, BSI lead to longer 
hospital stays and hence, additional costs [Turpin et al., 2011].  
Although most PN related BSI are caused by the intravenous catheter, numerous manipulations 
on the infusion unit may multiply the hazard of extrinsic contaminations [Didier et al., 1998]. 
To reduce this well-known risk, the relevant phases of PN (production, adding of supplements, 
administration) are subject to highest standards of hygiene in order to minimize the 
contamination risk. Industrial PN is manufactured following the guidelines of Good 
Manufacturing Practice (GMP) and under clean room conditions which reduces the 
contamination hazard significantly. Data indicate advantages of industrially manufactured PN 
compared to pharmacy-compounded PN formulations in terms of safety, however the limited 
data do not allow a definite conclusion [Turpin et al., 2012]. 
 
Blood glucose levels and ketogenic diets are a contentious issue and subject of controversial 
discussion among oncologists. In the 1920s, Nobel laureate Otto Warburg observed that unlike 
healthy body cells, cancer cells strongly upregulate the glucose intake to produce energy 
preferably via glycolysis, instead of the much more efficient way of oxidative phosphorylation 
[Liberti and Locasane, 2016]. This phenomenon is known as the Warburg-Effect. Data 
prudently suggest that carbohydrate restriction and ketogenic diets possibly obstruct cancer 
growths [Klement and Kaemmerer, 2016], however, too few clinical data is available to come 
to a definite conclusion. Due to the low level of evidence, the ESPEN guidelines 2017 
encourages further research on the effect of high fat diets on clinical outcome in patients with 
systemic inflammation and generally the effect of varying the fat [ESPEN guidelines, 2017, p. 
21]. 

 
 
 
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3.3 
Parenteral nutrition  
Parenteral nutrition is a sterile, liquid formula that is administered through an intravenous 
catheter directly into the bloodstream. It bypasses the normal digestion of the gastro-intestinal 
tract and may contain all necessary nutrients such as carbohydrate, protein, fat, electrolytes, 
(trace) minerals and vitamins. Various diseases and conditions that impair food intake or 
nutrient absorption may require the partial or complete substitution of oral or enteral 
nourishment. Patients who underwent acute surgery, suffer from short bowel syndrome or 
gastro-intestinal fistulas as well as critically ill patients including cancer patients at risk of CC 
may (temporarily) depend on PN. The specific composition needs to be customized to the 
individual needs of the patient depending on several factors as age, height, weight, nutritional 
requirements, underlying disease and the ability to intake enteral nutrition. 
The most common product types used in parenteral nutrition are either industrially premixed 
multi-chamber (2/3-chamber) bags or pharmacy-compounded admixtures in a mono- or 2-
chamber bags. The third, latest development are 7-, 8- or 9-chamber bags (Eurotubes®). 
3.3.1 Traditional 2/3-chamber bags 
Traditional 2/3-chamber bags are widely used in the PN landscape. Two or three separate 
compartments provide a combination of amino acids, lipids, glucose and electrolytes. Typically, 
most supplements cannot be added to the premixed 2/3-chamber bags due to stability reasons 
and incompatibilities. Also, the individual requirements vary significantly. To fully meet the 
patients’ needs, additional substances and agents are injected via syringe into the infusion unit 
shortly before administration of the product. That causes extra steps within the preparation 
process and increases the risk of errors and contamination. In patients receiving PN at home, 
that final step is usually performed by the nursing service, a family member or the patient 
himself. It is critical to perform this procedure in an environment as sterile as possible to avoid 
contamination of the product. 
The industrially premixed formulation can be stored at room temperature for several months 
and is available in different admixtures to meet various patients’ needs. However, the addition 
of vitamins, drugs or other supplements shortly before administration is always necessary if the 
composition of the industrially manufactured bags do not meet the individual requirements, 
which is frequently the case. 

 
 
 
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3.3.2 Pharmacy-compounding 
The on-demand compounding comprises another possibility to customize the PN formulations 
and provide the optimal composition of all needed supplements and medical agents. Pharmacies 
or commercial compounding services offer the PN customization on-demand and deliver the 
required infusion units. If there are no restrictions in compatibility, stability and/or storage then 
as many substances as possible can be combined. However, at least the addition of vitamins 
still needs to be performed and the problem of additional manipulations before administration 
remains.  
3.3.3 Eurotubes® 
Eurotubes® have been developed in 2013 to offer fully individualized PN compounding under 
GMP standard without the need for further line or bag manipulation outside the controlled GMP 
environment. 
Depending on the patient’s nutritional requirements the PN’s composition may be considerably 
complex. Besides trace minerals, extra electrolytes and vitamins, additional medications may 
be necessary. The 7-,8- or 9-chamber bags provide six extra compartments to separately add 
further substances such as vitamins or pharmaceuticals in the needed quantity and without the 
risk of instability or incompatibilities. They are customized to the individual recipient and 
contain all prescribed nutrients or medical agents in a ready-to-use system. After mixing the 
individual compartments, the infusion unit is ready to be used without further preparation. The 
system can also be equipped with an integrated pump feeding set which is ventilated and does 
not require further manipulations. Depending on the patient’s general condition, it is easily 
possible to self-administer the bags without the assistance of a nursing service or family 
member. The subjects’ daily routine stays independent from the nursing service, which is 
presumed to increase personal independence and flexibility while decreasing the overall 
treatment costs. 
3.4 
Studies on parenteral nutrition and infection 
To the present day, multiple studies have been conducted comparing industrially manufactured 
bags versus pharmacy-compounded bags to investigate the correlation of CRBSI and PN in 
subjects malnourished due to various reasons, including but not limited to cancer anorexia 
cachexia. It has been sufficiently demonstrated that PN is associated with an increased hazard 
of CRBSI, consequently with a prolonged hospital stay and thus, with higher costs.  

 
 
 
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Pontes-Arruda et al. [Pontes-Arruda et al., 2012] compared industrially pre-mixed PN products 
to individually compounded bags (COM-group, fabricated either by the hospital’s pharmacy or 
a compounding service provider) in 403 patients in total. The subjects of the COM-group 
showed a higher incidence of BSI and CLABSI than the subjects receiving industrially pre-
mixed PN (BSI: 22,5 % vs. 16,8 %, p = 0,03 and CLABSI: 13,2 % vs. 10,3 % per 1.000 catheter 
days, p < 0,0001). This suggests an advantage in terms of safety of PN products that are 
manufactured under GMP standards, however the study neglects to investigate the individual 
contamination risks in all occurring phases (production, compounding, injection of 
supplements, administration) and consequently cannot isolate the primary source of the 
infections. 
Pounds et al. [Pounds et al., 2013] showed in a single center trial that subjects treated with 
pharmacy-compounded PN experienced more adverse drug reactions and metabolic 
abnormalities than subjects receiving premixed parenteral nutrition. 18% of the COM-group 
developed a severe sepsis vs. 12% in the comparator arm, however, the sample size of 50 
patients per cohort limits the significance and requires further investigations. 
The review of Turpin et al. [Turpin et al., 2014] evaluated the impact of parenteral nutrition 
preparation on BSI risk and costs in 1.995 patients in Germany and brings an interesting angle 
into the investigations: He evaluated the risk of BSI and the cost of PN by retrospectively 
reviewing data of patients receiving PN via either multi-chamber bags (MCB), single bottle or 
hospital compounded admixtures and correlated the type of PN to the hospital costs. In his 
research he also discovered that adding supplements to MCB on the ward almost doubles the 
BSI hazard (rate of BSI per 1.000 PN days in MCB without additions vs. with addition: 4,3 vs. 
8,5). These data suggest that the quantity of manipulations and injections at the infusion unit 
correlates with the number of BSI and associated Adverse Events. However, further 
prospective, randomized trials will be needed to confirm this implication. 
3.5 
Rationale for PEKANNUSS trial 
PN at home using traditional 2/3-chambers is associated with a significant limitation and burden 
to the patients, as they are dependent on home care and nursing for administering the PN and 
injection of the required nutrition compounds. PN is, therefore, associated with frequent 
manipulation at the peripheral or central intravenous device. Data indicate that less 
manipulation on the PN bags before actual application to the patient reduces the hazard of BSI, 
however, industrially premixed MCB are often unable to entirely meet the patients’ needs and 

 
 
 
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require additional injections of supplements. Multiple line manipulations are required to 
substitute several nutrition compounds, leading to a high risk of catheter related complications, 
and limiting subjects’ autonomy. Eurotubes® – as ready-to-use system – require less 
manipulations and are, therefore, expected to be associated with less complications. The 
Eurotubes® are already used in the clinical routine practice. However, there is no clear 
recommendation which type of bags should be used in cancer patients, as there are no clinical 
trials comparing Eurotubes® versus traditional bags with regards to safety, QoL and response 
to concomitant anti-cancer therapy. Therefore, further research with randomized controlled 
trials is urgently required. 
3.6 
The relevance of this study to current care and benefit-risk assessment 
As elaborated above, the CC patients could benefit from a higher QoL by preserving the 
subjects’ autonomy and ability to self-administer the PN infusions. 
Furthermore, CRI represent a serious complication in patients receiving PN, weakens the 
already impaired subject, potentially delays chemotherapy and thereby diminishes therapeutic 
success. If the Eurotubes® prove to be efficient in preventing CRI, PN could become safer, 
more efficient and hospitalization time could be abbreviated. 
The procedures used in this study (such as PN application, blood tests, use of a patient’s study 
diary and QoL questionnaires) are in line with the current standard of care or minimal 
interventional, respectively. 2/3-chamber bags and Eurotubes® used for PN are market-
approved infusion units with no experimental approach. 
There is no evidence of a negative impact of glucose-reduced nutrition on CC subjects and can 
therefore be tested for its potential inhibitory effect on tumor growth. 
Taken together, the risks emerging from participation in this clinical trial are acceptable, 
considering the anticipated direct benefits for a subset of patients and the impact of the study 
results on the future treatment of patients in the given indication. 
 
 

 
 
 
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4 Study design 
This is an open-label, randomized, multicenter, investigator-initiated, phase IV trial. A total 
number of 216 patients will be enrolled (see chapter 7 for statistical calculations). 
Patients with metastatic or localized solid tumors who fulfil the eligibility criteria and who have 
an indication for parenteral nutrition will be enrolled.  
Patients will be stratified according to ECOG (0-1 vs. 2 vs. 3), the modified Glasgow Prognostic 
Score (mGPS) (0-1 vs. 2) and whether the patient receives concurrent systemic anti-cancer 
treatment (e.g. chemotherapy, targeted therapy, immunotherapy) or not. 
In a first step, patients will be randomized in a 2:1 ratio to Arm A or Arm B: 
Arm A: Standard Parenteral Nutrition using Eurotubes®. 
or 
Arm B: Standard Parenteral Nutrition using 2/3-chamber bags. 
Patients randomized to Arm B will receive PN according to the routine used by the 
participating site. 
Patients in Arm A will be stratified again by the same criteria as listed above and randomized 
in a 1:1 ratio to Arm A-1 or Arm A-2: 
Arm A-1: Standard Low Glucose Parenteral Nutrition using Eurotubes®. 
Patients randomized to Arm A and in a second randomization to treatment Arm A-1 
receive PN reduced in glucose in Eurotubes®. 
or 
Arm A-2: Standard Parenteral Nutrition using Eurotubes®. 
Patients randomized to Arm A and in a second randomization to treatment Arm A-2 will 
receive standard PN in Eurotubes®. 
Patients will be recruited during regular consultation visits. 
An overview of the study scheme is given in Figure 1. 

 
 
 
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Figure 1: Study Scheme. 

 
 
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At screening and at all regular visits during the HPN treatment period (one visit per four-week 
interval after randomization for a maximum of 12 months) the ECOG performance status and 
body weight will be determined. Additionally, physical examinations and laboratory 
assessments including CRP, albumin and total protein levels will be performed. Laboratory 
assessments do not need to be repeated at screening if laboratory assessments were done prior 
to screening within clinical routine and results are not older than 2 weeks. The type of catheter 
used for parenteral nutrition will be documented (Port-a-Cath, Hickmann/Broviac catheter etc).  
The HPN therapy and any modifications and adjustments to this plan during the course of HPN 
treatment will be recorded from visit 1 onwards. 
Anti-cancer treatment at the time of screening and any changes during the course of the HPN 
treatment period (e.g. type of treatment) will be documented. 
Monitoring of Adverse Events and medical device deficiencies will be performed at every visit. 
AEs will be graded according to the National Cancer Institute’s Common Terminology Criteria 
for Adverse Events (NCI CTCAE) version 5.0. 
During the study the patient will maintain a study diary to document details of the 
administration of the HPN. A QoL questionnaire will be completed during regular study visits 
until EOT.  
After completion of study treatment, patients will enter the follow-up period. During this period, 
they will be followed approximately every 3 months for survival which can be done by phone. 
 
 

 
 
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5 Objectives and Endpoints 
5.1 
Objectives 
5.1.1 Primary objective 
Patient autonomy  
To compare the frequency of self-administered parenteral nutrition at home (HPN) (autonomy 
rate) in patients with metastatic or localized solid tumors receiving standard parenteral nutrition 
through Eurotubes® versus traditional 2/3-chamber bags in the intent to treat population (ITT). 
5.1.2 Secondary Objectives 
Secondary Objectives 
• To compare the incidence of catheter related infections (CRI) between treatment Arms 
A and B in the per protocol population. 
• To compare the efficacy of PN in terms of body weight, C-reactive protein (CRP) and 
albumin levels, and overall survival (OS) 
• To compare the Quality of life (QoL) by use of the MODIFIED HPN-PROQ 
questionnaire 
• To determine the frequency of PN-related visits by the nursing service 
• To compare the safety in terms of the incidence of other catheter related complications, 
severe, common toxicity criteria (CTC) grade 3-5 infections, and PN-related Adverse 
Events (AEs) 
Secondary Objectives (Arm A-1 vs. A-2) 
• To compare the incidence of catheter related infections (CRI) 
• To compare the efficacy of PN in terms of body weight, C-reactive protein (CRP) and 
albumin levels, and overall survival (OS) 
• To compare the Quality of life (QoL) by use of the MODIFIED HPN-PROQ 
questionnaire 
• To compare the safety in terms of the incidence of other catheter related complications, 
severe, common toxicity criteria (CTC) grade 3-5 infections, and PN-related Adverse 
Events (AEs) 
5.2 
Endpoints 
5.2.1 Primary endpoint 
Patients’ autonomy  

 
 
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The rate of self-administered parenteral nutrition at home (autonomy rate), defined as 
administration without nursing service assistance, as documented within the patient’s study 
diary and calculated as the number of patients with autonomy divided by the total number of 
patients in the respective arm. Autonomy – as relevant for the primary endpoint – is achieved 
if the patient self-administers 70% or more of her/his total administrations (Note: Help of family 
members or other personal caregivers accounts for self-administration).     
5.2.2 Secondary endpoints 
Efficacy endpoints 
• Relative weight change determined at baseline and during study visits approx. every 
four weeks after enrolment; 
• Relative change of albumin and CRP levels measured at baseline and during regular 
study visits; 
• Overall survival (OS) defined as the time from randomization to death from any cause. 
Quality of Life endpoints  
• Quality of Life (QoL) through the MODIFIED HPN-PROQ questionnaire;  
• To determine the frequency of PN-related visits by the nursing service 
 
 
Safety endpoints 
• Catheter related infections (CRI) defined as the presence of bacteraemia originating 
from the intravenous (port) catheter – Bacteraemia must be confirmed through a blood 
culture according to study site-specific routine, preferably through paired quantitative 
blood cultures or a culture of the catheter if the catheter is removed – OR any 
infections originating from the intravenous (port) catheter, requiring intravenous 
antibiotics OR infections in the intravenous (port) catheter, requiring intravenous 
antibiotics or antibiotics delivered to the catheter itself or catheter removal. 
For the diagnostic procedures to be done to confirm CRI, investigators are 
recommended to follow the DGHO guidelines. 
• Catheter related complications such as line occlusions of catheter-related central 
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• Severe, NCI-CTC common toxicity criteria version 5.0 grade 3-5, infections including 
fever of unknown origin and other Adverse Events according to NCI-CTC common 
toxicity criteria version 5.0; 
• PN-Related Adverse Events (AEs) and hospitalizations during therapy; 
6 Statistical design 
The present trial is designed as an open-label, randomized, multicenter, investigator-initiated 
phase IV trial comparing standard parenteral nutrition using Eurotubes® vs. traditional 2/3-
chamber bags in subjects with metastatic or localized solid tumors requiring parenteral 
nutrition.  
The primary endpoint is defined as the frequency of self-administered HPN (patients’ 
autonomy). 
6.1 
Sample size calculation 
For the primary endpoint statistical significance is assessed using a fisher’s exact test at a two-
sided alpha level of 0.05 for the objective patient autonomy.  
The power calculation was carried out using the Power Procedure in SAS version 9.4 (method: 
Walters normal approximation for unbalanced groups): Considering the 2:1 randomization, 128 
patients must be included in Arm A (Standard Parenteral Nutrition using Eurotubes®) and 64 
patients in Arm B (Standard Parenteral Nutrition using 2/3-chamber bags), resulting in a sample 
size of 192 patients,  to ensure 80% power to detect an improvement of the objective patient 
autonomy from 5% with traditional 2/3-chamber bags to 20% with Eurotubes®.  
Assuming a dropout rate of about 10% it is planned to include 216patients.  
6.2 
Study Duration 
Each patient will receive study-specific PN for a maximum of 12 months starting from the 
date of randomization. Physicians are free to continue PN after the end of this 12 months 
period if they believe that PN is in the best interest of the patients, but this is done outside the 
study and is captured in the eCRF as post-discontinuation therapy. 
Recruitment is expected to occur over 3 years, followed by a maximum treatment duration of 
12 months within the trial and a 6 months period for data cleaning and monitoring resulting in 

 
 
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an expected total study duration of approximately 4.5 years. The study will be conducted at up 
to 50 sites located in Germany. 
6.3 
Analysis 
Prior to final analysis, data verification with respect to completeness and plausibility (data 
cleaning) will be performed. Inconsistencies and mistakes will be clarified with the study sites 
and will be removed. The data cleaning process starts soon after first patients are enrolled and 
monitored. Major protocol violations and special cases will be listed.  
After enrolment of 100 patientsan interim analysis will be performed, non-including the 
primary endpoint. 
The study analysis plan (SAP) and the handling of special cases and major violations will be 
defined and completed prior to study completion and prior to any conduct of analyses. 
6.3.1 Study populations for the analysis 
The following data sets for analysis are defined:  
 
Intent-to-treat population (ITT) 
The intent-to-treat (ITT) population includes all patients who were randomized. Treatment 
assignment is based on the randomized treatment (primary population). 
The ITT population is the primary population for the description of the patient and treatment 
characteristics and is used for the primary efficacy analysis.  
 
Per protocol (PP) population 
This population will include all randomized patients who fulfill the inclusion and exclusion 
criteria and received at least two weeks of PN at home according to treatment arm. Treatment 
assignment is based on the treatment actually given. Sensitivity analyses of the primary 
endpoint will be performed on the per protocol analysis set. 
 
Safety analysis set 
The evaluation of safety parameters is carried out in the safety population, which is defined as 
all randomized patients who received at least one application of PN at home. Treatment 
assignment is based on the treatment actually given. 
 

 
 
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Several subgroup analyses will be performed including but not limited to NRS score, ECOG 
classification and whether the patient receives concomitant anti-cancer therapy or not. Further 
details will be specified in the SAP. 
 
 
6.3.2 Statistical methods for the analysis 
Patient Demographics/Other Baseline Characteristics 
The following demographic and baseline characteristics will be summarized descriptively by 
treatment group: 
• Gender and age; 
• Patients’ disease (e.g. colon cancer, breast cancer, gastric cancer); 
• Tumor status (localized or metastatic solid tumors); 
• Number and type of organs involved in metastatic disease (e.g. liver, lung, lymph nodes, 
bone); 
• Patients history (concomitant disease, number and type of previous anti-cancer 
therapies); 
• Type and start date of the current/concomitant anti-cancer therapy; 
• ECOG performance status; 
• mGPS 
• Nutrition risk screening score; 
• Baseline lab values and baseline QoL; 
• Other characteristics. 
• Type of central catheter used for parenteral nutrition 
 
Primary Endpoint 
The primary analysis will compare patients randomized to Arm A (Standard Parenteral 
Nutrition using Eurotubes®) with those randomized to Arm B (Standard Parenteral Nutrition 
using 2/3-chamber bags) regarding the objective patient autonomy and will be based on the ITT 
population. To test the hypothesis: 
H01: “The objective patient autonomy does not differ between the treatment Arms A and B 
(P12 = P22).” 
vs. 

 
 
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H11: “The objective patient autonomy differs between the treatment Arms A and B 
(P12 ≠ P22).” 
fisher’s exact test is used with a type I error of 0.05.  
Secondary Endpoints 
All secondary analyses, excluding safety endpoints analyses, which will be based on the safety 
population, and the CRI, which will be based on the per protocol population, will be based on 
the ITT population. Sensitivity analysis of the primary endpoint and other important endpoints 
will be performed in the per protocol population, also. The parameters will be evaluated in an 
explorative manner, providing means, medians, ranges, standard deviations and/or confidence 
intervals. Rates will be compared using fisher’s exact test and continuous variables using t-test. 
For the time-to-event variable OS, the Kaplan-Meier method will be used, and treatment groups 
will be compared using a log rank test. All resulting p-values for secondary endpoints will be 
considered descriptive and will be presented explicitly without referring to hypotheses or a 
significance level. Usually, no p-value adjustment for multiple-testing will be performed. Thus, 
the p-values will reflect the comparison-wise error and not the experiment-wise error. All p-
values will be two-sided if not stated otherwise. The statistical methods described in this section 
are suited for the data and distributions usually expected in this type of trials. The suitability 
will be checked and if necessary, the statistical method will be modified accordingly, with 
critical discussion of the original and modified results. 
Further details of the planned procedures and specific analyses will be defined in the statistical 
analysis plan, latest prior to locking the database. 
7 Patient Selection 
7.1 
Inclusion Criteria 
Patients* must meet the following criteria to be eligible for the study: 
1. Age ≥ 18 years 
2. Histologically confirmed metastatic or localized solid tumor. Perioperative setting of 
HPN is allowed if HPN is planned for a duration of ≥ 2 months 
3. ECOG performance status of 0, 1, 2 or 3 
4. Indication for PN (the subject needs a PN independent of the trial) 
5. PN planned for 3 or more days per week 
6. Negative pregnancy test in women of childbearing potential 
7. Willingness to perform double-barrier contraception during study for women of 
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8. Willingness to maintain a study diary 
9. Life expectancy > 3 months 
10. Written informed consent 
*There are no data that indicate special gender distribution. Therefore, patients will be enrolled 
in the study gender-independently. 
 
7.2 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
1. > 4 weeks of consecutive (3 ≥ days per week) parenteral nutrition in the last 3 months 
prior to study enrolment 
2. Participation in another interventional clinical trial that could influence the endpoints 
of this trial or planned participation in such a study at the same time as this study is 
active (participation in other trials is possible in the follow up time for OS). The study 
is active, if the patients receive study treatment (PN), did not discontinue the trial for 
other reasons, and is still within the 12 months active study period 
3. Current catheter related infection at baseline. In patients with a suspected/proven 
previous conservatively managed catheter-related infection, a negative pair of blood 
cultures drawn from the central catheter is required. 
4. Pregnancy or breastfeeding 
5. Known hypertriglyceridemia ≥ CTCAE grade 3  
6. Unable or unwilling to provide written informed consent and to comply with the study 
protocol  
7. Uncontrolled diabetes mellitus  
8. Congestive heart failure NYHA ≥ 3 
9. Renal insufficiency GFR < 30 ml/min 
10. Uncontrolled infection 
11. Liver insufficiency 
8 Therapy scheme 
The S3-Guideline of the German Society for Nutritional Medicine for Clinical Nutrition in 
Oncology should be used as guidance when setting-up the PN therapy plan [S3-Guideline of the 
German Society for Nutritional Medicine (DGEM) in Cooperation with the DGHO, the ASORS 
and the AKE, Clinical Nutrition in Oncology]. 
The following must always be considered before determining the patient’s therapy scheme: 
• For all treatment arms the composition of the nutrients can differ from the tables below 
due to site-specific routine or investigator’s/medical decision. 

 
 
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• The frequency of PN is not pre-determined for any treatment arm and can change during 
the course of the study based on the evolving nutritional status of the patient.  
• The recommended infusion duration is 12-14 hours. However, the duration can differ and 
the maximum infusion speed per macronutrient should always be considered.  
• If the run-in phase was not conducted at the inpatient facility, then a low energy nutrition 
should be considered for the start of HPN to avoid a refeeding syndrome. 
• For Arm A-1 and Arm A-2 some modifications to the initially considered therapy plan 
might become necessary based on to the randomization results. These modifications 
should only be done if medically acceptable. 
Note: Any existent clinical contraindications must always be of overriding importance 
compared to the randomization results and therapy as randomized should only be 
administered if medically acceptable. 
 
Arm A-1: Standard Low Glucose Parenteral Nutrition using Eurotubes® 
Patients randomized to treatment Arm A-1 will receive PN reduced in glucose in Eurotubes® 
(Eurozyto). 
The following displays a guidance for the PN composition administered in Arm A-1. The 
amounts listed are understood as daily dose. Underlying medical conditions, intolerance etc. 
must always be considered per individual patient. 
 
Macronutrients: 
For the macronutrients, body weight is understood as the ideal body weight for the patient 
according to a BMI of 19 – 24 for women and 20 – 25 for men. 
Glucose:  
 
1.0 – < 2.0 g per kg body weight 
Amino acids:   
1.2 – 1.5 g per kg body weight 
Lipids:  
 
0.5 – 2.0 g per kg body weight 
 
 
 
Micronutrients: 
Independent of the ideal body weight, should be added taken the actual serum levels into 
account. 
Sodium: 
 
60 – 150 mmol 
Potassium: 
 
40 – 100 mmol 

 
 
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Magnesium:  
4 – 12 mmol 
Calcium: 
 
2.5 – 7.5 mmol 
Phosphate:  
 
10 – 30 mmol 
 
 
Trace Elements and Vitamins: 
Trace Elements and Vitamins are added according to the standard dietary reference intake. 
 
Water:  
 
 
The amount of water depends on the oral intake of water, volume tolerance and kidney function. 
As general guidance 30 – 40 ml per kg body weight should be considered. 
TOTAL: 
Total Volume: 
30 – 40 ml per kg body weight 
Total Calories:  
25 – 30 kcal per kg body weight 
 
 
 
 
guidance for calculating calories:  
 
 
 
 
1 g glucose ~ 4 kcal 
 
 
 
 
1 g amino acids ~ 4 kcal 
 
 
 
 
1 g lipids ~ 10 kcal 
 
The investigator should specify the PN composition according to the site-specific routine in 
consultation with a nutritional expert, if routinely involved in the PN at this site, considering 
the guidance above. At the investigator’s discretion he/she can also consult the Care 
Management/Supply Management of LIGETIS for advice and fine-tuning the PN composition. 
 
Arm A-2: Standard Parenteral Nutrition using Eurotubes® 
Patients randomized to treatment Arm A-2 will receive standard PN in Eurotubes® (Eurozyto). 
The following displays the specifications for the PN composition administered in Arm A-2. 
The amounts listed are understood as daily dose. Underlying medical conditions, intolerance 
etc. must always be considered per individual patient. 
 
Macronutrients: 
For the macronutrients, body weight is understood as the ideal body weight for the patient 
according to a BMI of 19 – 24 for women and 20 – 25 for men. 
Glucose:  
 
≥2.0 – 4.0 g per kg body weight 

 
 
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Amino acids:   
1.2 – 1.5 g per kg body weight 
Lipids:  
 
0.5 – 2.0 g per kg body weight 
 
Micronutrients: 
Independent of the ideal body weight, should be added taken the actual serum levels into 
account. 
Sodium: 
 
60 – 150 mmol 
Potassium: 
 
40 – 100 mmol 
Magnesium:  
4 – 12 mmol 
Calcium: 
 
2.5 – 7.5 mmol 
Phosphate:  
 
10 – 30 mmol 
 
Trace Elements and Vitamins: 
Trace Elements and Vitamins are added according to the standard dietary reference intake. 
 
Water: 
The amount of water depends on the oral intake of water, volume tolerance and kidney function. 
As general guidance 30 – 40 ml per kg body weight should be considered. 
 
TOTAL: 
Total Volume: 
30 – 40 ml per kg body weight 
Total Calories:  
25 – 30 kcal per kg body weight 
 
 
 
 
guidance for calculating calories:  
 
 
 
 
1 g glucose ~ 4 kcal 
 
 
 
 
1 g amino acids ~ 4 kcal 
 
 
 
 
1 g lipids ~ 10 kcal 
 
The investigator should specify the PN composition according to the site-specific routine in 
consultation with a nutritional expert, if routinely involved in the PN at this site, considering 
the guidance above. At the investigator’s discretion he/she can also consult the Care 
Management/Supply Management of LIGETIS for advice and fine-tuning the PN composition. 
 
Arm B: Standard Parenteral Nutrition using 2/3-chamber bags 

 
 
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Patients randomized to Arm B will receive standard PN using 2/3-chamber bags (various 
manufactures) according to the routine used by the participating site. 
The following displays a guidance for the PN composition administered in Arm B. The amounts 
listed are understood as daily dose. Underlying medical conditions, intolerance etc. must always 
be considered per individual patient. 
 
Macronutrients: 
For the macronutrients, body weight is understood as the ideal body weight for the patient 
according to a BMI of 19 – 24 for women and 20 – 25 for men. 
Glucose:  
 
≥2.0 – 4.0 g per kg body weight 
Amino acids:   
1.2 – 1.5 g per kg body weight 
Lipids:  
 
0.5 – 2.0 g per kg body weight 
 
Micronutrients: 
Independent of the ideal body weight, should be added taken the actual serum levels into 
account. 
Sodium: 
 
60 – 150 mmol 
Potassium: 
 
40 – 100 mmol 
Magnesium:  
4 – 12 mmol 
Calcium: 
 
2.5 – 7.5 mmol 
Phosphate:  
 
10 – 30 mmol 
 
Trace Elements and Vitamins: 
Trace Elements and Vitamins are added according to the standard dietary reference intake. 
 
Water: 
The amount of water depends on the oral intake of water, volume tolerance and kidney function. 
As general guidance 30 – 40 ml per kg body weight should be considered. 
 
TOTAL: 
Total Volume: 
30 – 40 ml per kg body weight 
Total Calories:  
25 – 30 kcal per kg body weight 
 
 
 
 
guidance for calculating calories: 
 
 
 
 
1 g glucose ~ 4 kcal 

 
 
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1 g amino acids ~ 4 kcal 
 
 
 
 
1 g lipids ~ 10 kcal 
 
The investigator should specify the PN composition according to the site-specific routine in 
consultation with a nutritional expert, if routinely involved in the PN at this site, considering 
the guidance above. The investigator is free to use any manufacturer of traditional 2/3-chamber 
bags but should follow the site-specific routine. At the investigator’s discretion he/she can also 
consult the Care Management/Supply Management of the respective manufacturer or of 
LIGETIS. Examples of manufactures providing 2/3-chamber bags are Braun (Nutriflex 
portfolio), Fresenius (SMOF Kabiven or Kabiven portfolio) or Baxter (Olimel portfolio). 
 
 

 
 
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9 Treatment schedule and schedule of assessments 
The treatment schedule is displayed in Figure 4. 
 
Figure 2: Treatment schedule and schedule of assessments. 
* The indication for PN will usually come from a physician during routine treatment in a hospital inpatient or outpatient setting and should be given independent of the trial.. The patient might have 
started PN already during routine (inpatient) treatment. PN=Parenteral nutrition (here: potential run-in phase); ET-G= standard low glucose HPN in Eurotubes®; ET= standard HPN in Eurotubes®; 
2/3=standard HPN in 2/3-chamber bags; HPN=Home Parenteral nutrition in any PN bag; w=week; m=month, yr=year. 
Please note: the protocol visits may be less frequent than the medically indicated visits. Please schedule visits as it is usual in your study site independent of the study but at least as frequent 
as indicated in this protocol. Reportable events occurring in other visits (scheduled or unscheduled) other than those required here should be reported in the eCRF with the documentation of 
the subsequent protocol visits. 

 
 
 
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9.1 
Schedule of assessments  
The schedule of assessments is displayed in Table 1. The assessments are the same irrespective 
of the treatment arm. 
Table 1: Schedule of Assessments 
Schedule of Assessments 
Screening 
Visit 1 – 
Visit 121 
EOT 
Visit 
Follow-
Up2 
Informed consent3 
X 
 
 
 
ECOG 
X4 
X 
X16 
 
Modified Glasgow Prognostic Score (mGPS) 
X4 
X 
X 
 
Nutritional Risk Screening 
X4 
 
 
 
Physical Examination 
X 
X 
X16 
 
Weight 
X 
X 
X16 
 
Height 
X 
 
 
 
Medical History 
X 
 
 
 
Demographics, other baseline parameters 
X 
 
 
 
Concomitant anti-cancer therapy (if any) 
X5 
X6 
X6 
 
Laboratory7 
X 
X 
X 
 
Pregnancy test8 
X 
 
 
 
Catheter Related Infections (CRI) 
X 
X 
X 
 
Any catheter related complications 
X 
X 
X 
 
 Adverse Events9 
X 
X 
X 
(X) 
 Medical device deficiencies10 
 
X 
X 
 
QoL questionnaire11 
X 
X 
X16 
 
Patient’s study diary 
X12 
X13 
X13 
 
HPN therapy plan / administration/documentation 
 
X14 
X14 
 
Post discontinuation PN 
 
 
 
X15 
Overall survival 
 
X 
X 
X 
 
(1) 
A maximum of 12 visits should be documented within the study. The visit schedule itself is up to 
the clinical routine at the site and may occur approx. every four weeks. However, only the first 
visit within each four-week interval (starting from randomization) will be documented. If there is 
more than one visit within a four-week interval, only the first visit will be documented.  
(2) 
Every 3 months (+/- 2 weeks) until death or end of the study for survival status. 
(3) 
Mandatory prior to any study procedure. 
(4) 
Should be (re-)determined by the study personnel even if known through the documentation 
received by the inpatient facility. Please note: ECOG PS of 0, 1, 2 and 3 are eligible for the trial. 
(5) 
Any anti-cancer therapy (including surgery and radiation) should be documented. 
(6) 
Changes in the anti-cancer therapy should be documented  
(7) 
Routine peripheral blood lab usually done in patients receiving HPN including but not limited to: 
Complete blood count (German: kleines Blutbild), albumin, total protein level (German: 
Gesamteiweiß), CRP, GOT (AST), GPT (ALT), LDH, cholinesterase, creatinine, triglycerides, 
urea, glucose, electrolytes (sodium, potassium, magnesium, calcium, phosphate) should be 

 
 
 
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determined according to local lab routine. Laboratory assessments do not need to be repeated at 
screening if laboratory assessments were done prior to screening within clinical routine and results 
are not older than 2 weeks. 
(8) 
In case of women of child-bearing potential. Serum pregnancy test at Screening. 
(9) 
Adverse Events (related or not) are captured at any time throughout the study as soon as they 
become known to the study team, beginning after the patient has given written informed consent 
and up to 14 days after the last study treatment was administered. 
(10) 
Medical device deficiencies are captured from randomization until last study specific HPN. 
(11) 
The site staff instructs the patient of how to complete the QoL questionnaire. Questionnaire is 
completed during all documented study visit until EOT. Results of the completed QoL 
questionnaire(s) are transcribed to the eCRF by the site. 
(12) 
The site staff instructs the patient how to complete the patient’s study diary. Handing out of a 
diary covering enough days until the next planned visit. Patient should complete diary daily until 
EOT. Please note: patients’ diary is very important as it includes information on one of the 
study primary endpoint!   
(13) 
Results of the completed study diary are transcribed to the eCRF. Handing out of new diaries as 
needed. 
(14) 
Adjustments of the PN therapy plan are possible throughout the study, independent from the 
planned study visits. The latest adjustment will be documented at the time of each visit. The PN 
is administered at home through the nursing service, a caregiver or the patient. 
(15) 
After EOT, subsequent HPN/PN will be captured (only manufacturer). 
(16) 
If results of examinations are available which are not older than 14 days no further examination 
will be necessary. 
 
Important note: These assessments are required by the study protocol. All examinations are part of 
routine clinical practice. It is important to note that the study protocol does not limit the examinations 
to the points mentioned above. The investigator shall perform all other/additional routine or site-specific 
examinations relevant to the safety of the patient or for any other procedures done. 
 

 
 
 
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10 References 
Arends J, Bertz H, Bischoff SC, Fietkau R, Herrmann HJ, Holm E, Horneber M, Hütterer E, Körber J, Schmid I 
and the DGEM Steering Committee. S3-Leitline der Deutschen Gesellschaft für Ernährungsmedizin e. V. 
(DGEM) in Kooperation mit der Deutschen Gesellschaft für Hämatologie und Onkologie e. V. (DGHO), der 
Arbeitsgemeinschaft „Supportive Maßnahmen in der Onkologie, Rehabilitation und Sozialmedizin“ der 
Deutschen Krebsgesellschaft (ASORS) und der Österreichischen Arbeitsgemeinschaft für klinische Ernährung 
(AKE). Aktuel Ernahrungsmed 2015; 40: e1–e74 
 
Arends J et al. "ESPEN guidelines on nutrition in cancer patients." Clinical Nutrition 36.1 (2017): 11-48. 
 
Bauer JD, Capra S. Nutrition intervention improves outcomes in patients with cancer cachexia receiving 
chemotherapy - a pilot study. Support Care Cancer 2005;13:270-4. 
 
Beghetto MG, Victorino J, Teixeira L, de Azevedo MJ. Parenteral nutrition as a risk factor for central venous 
catheter–related infection. JPEN J Parenter Enteral Nutr. 2005; 29(5), 367-373. 
 
Bossola M, Pacelli F, Tortorelli A, Doglietto GB. Cancer cachexia: it's time for more clinical trials. Ann Surg 
Oncol. 2007;14:276-85. 
 
Caccialanza R et al. "Early 7-day supplemental parenteral nutrition improves body composition and muscle 
strength in hypophagic cancer patients at nutritional risk." Supportive Care in Cancer (2018): 1-10. 
 
Canada T, Turpin R, Williams K, Scott S. Blood-stream infections and their attributable length of stay: Does 
delivery of parenteral nutrition via multi-chamber bag have any impact? Paper presented at: American College of 
Clinical Pharmacy Annual Meeting. Anaheim, CA (2009) 
 
Didier ME, Fischer S, Maki DG. Total nutrient admixtures appear safer than lipid emulsion alone as regards 
microbial contamination: growth properties of microbial pathogens at room temperature. JPEN J Parenter 
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Dissanaike S, Shelton M, Warner K, O’Keefe GE. The risk for bloodstream infections is associated with 
increased parenteral caloric intake in patients receiving parenteral nutrition. Crit Care. 2007;11(5):R114. 
 
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, 
Mantovani G, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 
2011 May;12(5):489-95. 
 
Hentrich et al. ZVK Infektionen, Onkopedia Guideline, DGHO July 2015 
 
Klement RJ, Kaemmerer U. Can a Low Carbohydrate/ketogenic Diet Retard Tumor Growth? Aktuel 
Ernahrungsmed. 2016; 41(2), 95-102. 
 
Kondrup J, Allison SP, Elia M, Vellas B, Plauth M; Educational and Clinical Practice Committee, European 
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