Efficacy Study of Long-term Parenteral Nutrition With SmofKabiven® E in Lung Cancer Patients Under Anticancer Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of long-term addition of SmofKabiven® E to normal oral nutrition after routine dietary counseling as compared to standard of care nutrition in which oral nutrition is the primary nutritional support. It takes place in lung cancer patients under chemo- and/or immunotherapy. Efficacy will be determined primarily by calculating the change of patient's body weight from before start of study treatment to end of treatment, and comparing this change between both treatment groups.

Official Title
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Efficacy of Long-term Parenteral Nutrition With SmofKabiven® E Concomitant to Chemo- and/or Immunotherapy: A Prospective, Randomised, Controlled, Open, Multicentre, Two-stage, Adaptive Clinical Trial in Metastatic Non-small Cell Lung Cancer

Conditions
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Cancer-related Malnutrition

Intervention / Treatment
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* Drug: SmofKabiven® E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic non-small cell lung cancer patient Adult ≥ 18 years Starting any 1st, 2nd or 3rd line chemotherapy and/or immunotherapy administered via a central venous catheter (including implanted ports), or receiving the 2nd cycle of aforementioned anticancer treatment An energy gap of ≥ 40 % and/or 1000 kcal between the target energy intake (30 ± 5 kcal/kg/day) and the actual energy intake at screening, irrespective of weight loss Functional digestive tract allowing oral intake If female of childbearing potential, willing to use a sufficiently safe contraception method throughout participation in the study Signed informed consent from patient or legal representative Exclusion Criteria: Parenteral nutrition (PN) administered during the preceding month (the sole administration of intravenous glucose is allowed), or standard of care PN planned to start within 3 weeks after baseline visit More than 1600 kcal/day required as PN Tube feeding at screening, or planned to start within 3 weeks after baseline visit Body mass index (BMI) > 30 kg/m2 Performance status > 3 Eastern Cooperative Oncology Group (ECOG) score Life expectancy < 3 months Active bloodstream infection demonstrated by positive blood culture at Screening Hypersensitivity to fish-, egg, soya- or peanut protein or to any of the active substances or excipients in SmofKabiven E Severe blood coagulation disorders Congenital errors of amino acid metabolism Pathologically elevated serum levels of any of the included electrolytes General contraindications to infusion therapy: acute pulmonary oedema, hyperhydration, decompensated cardiac insufficiency Hemophagocytotic Syndrome Severe hyperlipidemia (serum triglycerides > 353 mg/dL) Severe liver insufficiency: liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma glutamyl transferase [GGT]) or conjugated bilirubin exceeding 3 x upper limit of normal range, or International Normalised Ratio (INR) > 2 Severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 ml/min/1.73m2) and patients on renal replacement therapy Uncontrolled hyperglycaemia Unstable conditions (e.g., embolism, metabolic acidosis, hypotonic dehydration) Pregnancy or lactation Contraindications to any of the study assessment methods including computer tomography and indirect calorimetry Participation in a clinical study with an investigational drug or investigational medical device within one month prior to start of study or during study Prior inclusion in the present study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SmofKabiven® E + standard oral nutrition<br>SmofKabiven® E, with or without addition of Suppliven®, Vitalipid® Adult and/or Soluvit® will be administered at 5-7 days per week for up to 9 +/-1 weeks in addition to standard of care oral nutrition as per routine dietary counseling, to reach the patient's target energy intake. | Drug: SmofKabiven® E<br>* In the intervention arm, SmofKabiven® E, with or without addition of Suppliven®, Vitalipid® Adult and/or Soluvit®, will be administered in addition to standard of care oral nutrition as per dietary counseling, whereas in the control arm, oral nutrition as per dietary counseling is the primary nutritional support.<br>|
| No Intervention: Standard oral nutrition<br>The patients will consume standard of care oral nutrition as per routine dietary counseling, to reach their target energy intake. Standard of care tube feeding or parenteral nutrition is allowed to start earliest 3 weeks after baseline visit, if required. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total body weight (kg) |  | Every 2-3 weeks, for up to 9 +/-1 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum albumin |  | Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline | 
| Serum transthyretin |  | Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline | 
| Nutritional Risk Index |  | Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline | 
| Unplanned PN or tube feeding according to standard of care in control group |  | Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline | 
| Early termination of PN due to improvement in test group |  | Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline | 
| Lean body mass determined from computer tomography (CT) scan at 3rd lumbar vertebra |  | Baseline to final visit at 9 +/1 weeks after baseline | 
| Optional: lean tissue mass, phase angle and hydration status including intra- and extracellular body water with bioelectrical impedance analysis (BIA), if BIA device is available. |  | Baseline to final visit at 9 +/1 weeks after baseline | 
| Karnofsky performance status |  | Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline | 
| ECOG performance status |  | Time Frame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline | 
| Handgrip strength in kg, using hand dynamometer |  | Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline | 
| Actual and target number of completed chemotherapy and/or immunotherapy cycles |  | Every 2-3 weeks from baseline to 3 months after baseline | 
| Actual dose and target chemotherapy and/or immunotherapy dose administered |  | Every 2-3 weeks from baseline to 3 months after baseline | 
| Chemotherapy and/or immunotherapy toxicities according to NCI-CTC v4.0 including dose-limiting toxicities |  | Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline | 
| Fatigue using the brief fatigue inventory (BFI questionnaire) |  | Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline | 
| Overall survival |  | Until 6 months post baseline | 
| Progression-free survival |  | At 3 and 6 months post baseline | 
| Partial response rate (as per RECIST v 1.1) |  | At 9 +/-1 weeks, 3 months and 6 months after baseline | 
| Complete response rate (as per RECIST v 1.1) |  | At 9 +/-1 weeks, 3 months and 6 months after baseline | 
| Unplanned hospitalization |  | From baseline until 6 months after baseline | 
| Quality of life (Functional Assessment of Cancer Therapy- General [FACT-G] score) |  | From baseline until final visit at 9 +/-1 weeks after baseline | 
| Number of patients terminating anti-cancer and nutrition therapy as part of end-of-life care |  | From baseline until final visit at 9 +/-1 weeks after baseline | 
| Resting energy expenditure | measured by indirect calorimetry | From baseline until final visit at 9 +/-1 weeks after baseline | 
| Ocurrence of unplanned admission to nursing home |  | From baseline until final visit at 9 +/-1 weeks after baseline |