Clinical Trial Results:
Randomized phase III study: Supplemental parenteral nutrition for patients with locally advanced inoperable tumors of the head and neck, receiving definitive radiotherapy with Cetuximab or Cisplatin
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Summary
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EudraCT number |
2014-003833-24 |
Trial protocol |
AT |
Global end of trial date |
10 Jul 2019
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Results information
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Results version number |
v2(current) |
This version publication date |
25 Jul 2020
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First version publication date |
08 Jul 2020
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AGMT_HNO_PN
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02236936 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AGMT
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Sponsor organisation address |
Gentzgasse 60/21, Vienna, Austria, 1180
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Public contact |
Daniela Wolkersdorfer, AGMT, +43 6626404412, d.wolkersdorfer@agmt.at
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Scientific contact |
Richard Greil, AGMT, +43 5725525801, r.greil@salk.at
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 May 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Jul 2019
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Loss of body weight by more than 5% at the end of radiotherapy, compared with weight at the beginning of therapy, will be scored as an event of critical weight loss
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Protection of trial subjects |
Safety assessments were scheduled weekly during treatment and 3 months after end of radiation. Dose modifications in case of toxicity were described in the
protocol. Concomitant medications and therapies necessary for supportive care and safety of the patient were allowed. Only patients eligible for definitive curative radio-chemotherapy with Cisplatin or radio-immunotherapy with Cetuximab could have been included. The administration of concurrent other cancer therapy (chemotherapy, immunotherapy, antihormonal or biologic therapy) or concurrent treatment with an investigational drug was not permitted.
Women of childbearing potential must have a negative pregnancy test at screening and must use effective contraception.
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Background therapy |
Standard of care (Immunotherapy with cetuximab; chemotherapy with cisplatin; radiation therapy) | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Apr 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 8
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Worldwide total number of subjects |
8
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EEA total number of subjects |
8
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
First patient in (FPI): 20-Apr-2017; Last patient in (LPI): 02-Jul-2018; Recruitment was prematurely withdrawn on 10-July-2019 due to low recruitment. Assessed for eligibility: 21 patients Eligible and randomized: 8 patients, randomized at 3 different sites in Austria. | |||||||||
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Pre-assignment
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Screening details |
21 patients with histologically confirmed local advanced squamous cell carcinoma of the larynx, hypopharynx, oropharynx or cavum oris and definitly planned radiotherapy in combination with cisplatin or cetuximab were screened for eligibility. Only 8 patients met inclusion criteria and were willing to participate. | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm A - control | |||||||||
Arm description |
Standard of care with or without parenteral nutrition | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Arm B - intervention group | |||||||||
Arm description |
Parenteral overnight nutrition with ZentroOLIMEL® 5.7% with electrolytes, vitamins (Cernevit®) and micronutrients (Addel Trace® or Nutryelt®) 15 ml/kg body weight/day (weight loss >5% from baseline, parenteral nutrition has to be increased up to 25 ml/kg body weight per day) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
ZentroOLIMEL®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Parenteral overnight nutrition with ZentroOLIMEL® 5.7% with electrolytes, vitamins (Cernevit®) and micronutrients (Addel Trace® or Nutryelt®) starting with 15 ml/kg body weight/day. In case of weight loss of more than 5%, dose of ZentroOLIMEL® has to be increased up to 25 ml/kg/body weight/day. During the RTX period of 7 weeks, with a total of 49 days of parenteral nutritional support.
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Investigational medicinal product name |
Cernevit®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Parenteral overnight nutrition with ZentroOLIMEL® 5.7% with electrolytes, vitamins (Cernevit®) and micronutrients (Addel Trace®or Nutryelt®) starting with 15 ml/kg body weight/day. In case of weight loss of more than 5%, dose of ZentroOLIMEL® has to be increased up to 25 ml/kg/body weight/day. During the RTX period of 7 weeks, with a total of 49 days of parenteral nutritional support.
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Investigational medicinal product name |
Nutryelt® or Addel Trace®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Parenteral overnight nutrition with ZentroOLIMEL® 5.7% with electrolytes, vitamins (Cernevit®) and micronutrients (Addel Trace®or Nutryelt®) starting with 15 ml/kg body weight/day. In case of weight loss of more than 5%, dose of ZentroOLIMEL® has to be increased up to 25 ml/kg/body weight/day. During the RTX period of 7 weeks, with a total of 49 days of parenteral nutritional support.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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End points reporting groups
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Reporting group title |
Arm A - control
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Reporting group description |
Standard of care with or without parenteral nutrition | ||
Reporting group title |
Arm B - intervention group
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Reporting group description |
Parenteral overnight nutrition with ZentroOLIMEL® 5.7% with electrolytes, vitamins (Cernevit®) and micronutrients (Addel Trace® or Nutryelt®) 15 ml/kg body weight/day (weight loss >5% from baseline, parenteral nutrition has to be increased up to 25 ml/kg body weight per day) | ||
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End point title |
Critical weight loss (>5%) [1] | ||||||||||||
End point description |
Loss of body weight by more than 5% at the end of RTX, compared with weight at the beginning of therapy, is scored as an event of critical weight loss
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End point type |
Primary
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End point timeframe |
Difference between baseline and week 8 (after end of radiotherapy)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been specified, as recruitment was pematurely withdrawn and to less patients were recruited to perform statistical analyses. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All patients having received at least one dose of the study medication were followed for adverse events for at least 28 days after discontinuing study treatment or completion of study treatment.
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Adverse event reporting additional description |
Progression of disease (including death due to the underlying malignant disease) is not to be regarded as SAE.
Due to the seriousness of the disease in this study, certain conditions defined as SAEs were excluded from expedited reporting on a SAE report Form, i.e.:
Elective hospitalization and surgery for treatment of disease.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23
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Reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Jul 2018 |
Due to low recruitment, procedures and questionnaires were removed to simplify protocol procedures. Many patients refused participation due to long hospital stays during treatment within the study. To increase acceptance of treatment home-care systems are allowed to be used. To get early information about feasibility, tolerability and efficacy of treatment also in case of persisting low recruitment, interim analysis was established after randomization of 40 patients. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Statistical analyses according to protcol could not be performed as trial was stopped prematurely due to low recruitment on 10-Jul-2019. | |||
