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

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

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.

Study Overview

• Status: Terminated
• Conditions: Cancer-related Malnutrition
• Intervention / Treatment: Drug: SmofKabiven® E

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Hopital Cochin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SmofKabiven® E + standard oral nutrition; 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; 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.
No Intervention: Standard oral nutrition; 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?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Aspartate Aminotransferase	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Alanine Aminotransferase	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Alkaline phosphatase	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Gamma-Glutamyl Transferase	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Direct bilirubin	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Total bilirubin	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Internal Normalized Ratio	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum creatinine	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum urea	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum sodium	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum potassium	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum total calcium	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum magnesium	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum chloride	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum phosphate	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum bicarbonate	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum glucose	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Serum triglycerides	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Red blood cell count	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Total white blood cell count	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Differential blood count	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Haemoglobin	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Haematocrit	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Platelet count	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
C-reactive protein	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Blood pressure	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Heart rate	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Body temperature	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline
Infection rate including catheter-related blood stream infections demonstrated by positive blood culture	From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline

Collaborators and Investigators

• Sponsor: Fresenius Kabi
• Investigators: Principal Investigator: Jean-Philippe Durand, MD, Hôpital Cochin, PARIS

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2018
• Primary Completion (Actual): April 5, 2019
• Study Completion (Actual): April 5, 2019

Study Registration Dates

• First Submitted: November 16, 2017
• First Submitted That Met QC Criteria: November 21, 2017
• First Posted (Actual): November 28, 2017

Study Record Updates

• Last Update Posted (Actual): May 1, 2019
• Last Update Submitted That Met QC Criteria: April 29, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition
• Other Study ID Numbers: SMKV-013-CP4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No