Clinical trial NCT03355079: Efficacy Study of Long-term Parenteral Nutrition With SmofKabiven® E in Lung Cancer Patients Under Anticancer Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Cancer-related Malnutrition
Lead sponsor: Fresenius Kabi
Sponsor class: INDUSTRY
First posted: 2017-11-28
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in total body weight (kg)
timeFrame: Every 2-3 weeks, for up to 9 +/-1 weeks
Secondary outcomes:
measure: Serum albumin
timeFrame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline
measure: Serum transthyretin
timeFrame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline
measure: Nutritional Risk Index
timeFrame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline
measure: Unplanned PN or tube feeding according to standard of care in control group
timeFrame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline
measure: Early termination of PN due to improvement in test group
timeFrame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline
measure: Lean body mass determined from computer tomography (CT) scan at 3rd lumbar vertebra
timeFrame: Baseline to final visit at 9 +/1 weeks after baseline
measure: 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.
timeFrame: Baseline to final visit at 9 +/1 weeks after baseline
measure: Karnofsky performance status
timeFrame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline
measure: ECOG performance status
timeFrame: Time Frame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline
measure: Handgrip strength in kg, using hand dynamometer
timeFrame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline
measure: Actual and target number of completed chemotherapy and/or immunotherapy cycles
timeFrame: Every 2-3 weeks from baseline to 3 months after baseline
measure: Actual dose and target chemotherapy and/or immunotherapy dose administered
timeFrame: Every 2-3 weeks from baseline to 3 months after baseline
measure: Chemotherapy and/or immunotherapy toxicities according to NCI-CTC v4.0 including dose-limiting toxicities
timeFrame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline
measure: Fatigue using the brief fatigue inventory (BFI questionnaire)
timeFrame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline
measure: Overall survival
timeFrame: Until 6 months post baseline
measure: Progression-free survival
timeFrame: At 3 and 6 months post baseline
measure: Partial response rate (as per RECIST v 1.1)
timeFrame: At 9 +/-1 weeks, 3 months and 6 months after baseline
measure: Complete response rate (as per RECIST v 1.1)
timeFrame: At 9 +/-1 weeks, 3 months and 6 months after baseline
measure: Unplanned hospitalization
timeFrame: From baseline until 6 months after baseline
measure: Quality of life (Functional Assessment of Cancer Therapy- General [FACT-G] score)
timeFrame: From baseline until final visit at 9 +/-1 weeks after baseline
measure: Number of patients terminating anti-cancer and nutrition therapy as part of end-of-life care
timeFrame: From baseline until final visit at 9 +/-1 weeks after baseline
measure: Resting energy expenditure
timeFrame: From baseline until final visit at 9 +/-1 weeks after baseline
measure: Ocurrence of unplanned admission to nursing home
timeFrame: From baseline until final visit at 9 +/-1 weeks after baseline
Other outcomes:
measure: Aspartate Aminotransferase
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Alanine Aminotransferase
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Alkaline phosphatase
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Gamma-Glutamyl Transferase
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Direct bilirubin
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Total bilirubin
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Internal Normalized Ratio
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum creatinine
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum urea
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum sodium
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum potassium
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum total calcium
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum magnesium
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum chloride
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum phosphate
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum bicarbonate
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum glucose
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Serum triglycerides
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Red blood cell count
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Total white blood cell count
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Differential blood count
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Haemoglobin
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Haematocrit
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Platelet count
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: C-reactive protein
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Blood pressure
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Heart rate
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Body temperature
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
measure: Infection rate including catheter-related blood stream infections demonstrated by positive blood culture
timeFrame: From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Locations:
city: Paris
country: France
facility: Hôpital Cochin
Study officials:
affiliation: Hôpital Cochin, Paris
name: Jean-Philippe Durand, MD
role: PRINCIPAL_INVESTIGATOR
References: