Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

Study Overview
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Brief Summary
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Prevention of critical weight loss. In patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) weight loss is a relevant clinical problem during radiotherapy and might result in higher treatment related toxicity and discontinuation of a potential curative treatment. Thus the investigators want to evaluate the efficacy of overnight parenteral nutritional (PN) support in patients with SCCHN treated with curative radiotherapy (RTX) in combination with Cetuximab (E) or Cisplatin (P).

Detailed Description
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The investigators hypothesize that about 60% of patients receiving RTX without supplemental PN will suffer from critical weight loss of more than 5% during treatment - supplemental overnight PN might result in significant improvement of the nutritional status .

Official Title
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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

Conditions
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Squamous Cell Carcinoma of the Hypopharynx Stage III, Squamous Cell Carcinoma of the Hypopharynx Stage IV, Laryngeal Squamous Cell Carcinoma Stage III, Laryngeal Squamous Cell Carcinoma Stage IV, Oropharyngeal Squamous Cell Carcinoma Stage III, Oropharyngeal Squamous Cell Carcinoma Stage IV, Squamous Cell Carcinoma of the Oral Cavity Stage III, Squamous Cell Carcinoma of the Oral Cavity Stage IV, Locally Advanced Malignant Neoplasm

Intervention / Treatment
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* Dietary Supplement: Standard care of parenteral nutrition
* Dietary Supplement: Parenteral over night nutrition
* Biological: Cetuximab
* Drug: Cisplatin
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient who is eligible for definitive curative radio-chemotherapy with Cisplatin or radio-immunotherapy with Cetuximab. Written informed consent obtained prior to any study specific screening activities and patients have to be able to comply with this protocol. Histologically confirmed local advanced squamous cell carcinoma of the Larynx, Hypopharynx, Oropharynx or Cavum oris treated with definitive radiotherapy in combination with Cisplatin or Cetuximab. p16 status available Age ≥ 18 Women of childbearing potential must have a negative pregnancy test at screening and must use effective contraception. Exclusion Criteria: Distant metastases Prior radiation (Head and neck area) Pregnant or lactating women History of other malignancy; yet patients who have been disease-free for 5 years or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Concurrent other cancer therapy (chemotherapy, immunotherapy, antihormonal or biologic therapy) or concurrent treatment with an investigational drug. Serious medical or psychiatric disorders that would interfere with the patient's safety or informed consent. Participation in another interventional clinical study at time of study inclusion (except follow-up period without treatment for more than 30 days) or denial of the simultaneous participation in a non-interventional study by the PI of the study center.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A - Standard of care<br>Standard care of parenteral nutrition (with or without parenteral nutrition during radio-chemotherapy or radio-immunotherapy in combination with Cetuximab or Cisplatin. Concomitant radiotherapy and immunotherapy (radio-immunotherapy) with Cetuximab or concomitant radiotherapy and chemotherapy (radio-chemotherapy) with Cisplatin | Dietary Supplement: Standard care of parenteral nutrition<br>* Standard treatment according to the discretion of the center, any required nutritional support (enteral tube feeding by nasogastric tube or percutaneous endoscopic gastrostomy) when considered necessary is allowed<br>* Other names: PN;Biological: Cetuximab<br>* Weekly during radiotherapy; not given if cisplatin is given during radiotherapy Cetuximab 400 mg/m2 (saturation) Cetuximab 250mg/m2 (during radiotherapy; in total 7x)<br>* Other names: Erbitux;Drug: Cisplatin<br>* Cisplatin total dose of >200 mg administered weekly (40 mg/m2/week) or every three weeks (100 mg/m2 every three weeks) according to local standard; not given in combination with cetuximab<br>* Other names: CDDP;Radiation: Radiotherapy<br>* 70 Gy / 5 fractions per week, over 7 weeks<br>* Other names: RTX;|
| Experimental: Arm B - Parenteral over night nutrition<br>Parenteral over night nutrition with ZentroOLIMEL 5.7% parenteral over night with electrolytes, vitamins (Cernevit®) and micronutrients (Addel Trace® or Nutryelt®) 15 ml/kg body weight/day (weight loss >5% from baseline; parenteral nutrition increased up to 25 ml/kg body weight per day) during radio-chemotherapy or radio-immunotherapy in combination with Cetuximab or Cisplatin. Concomitant radiotherapy and immunotherapy (radio-immunotherapy) with Cetuximab or concomitant radiotherapy and chemotherapy (radio-chemotherapy) with Cisplatin | Dietary Supplement: Parenteral over night nutrition<br>* Patients in interventional Arm B will receive 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.<br>* Other names: Emulsion for infusion;Biological: Cetuximab<br>* Weekly during radiotherapy; not given if cisplatin is given during radiotherapy Cetuximab 400 mg/m2 (saturation) Cetuximab 250mg/m2 (during radiotherapy; in total 7x)<br>* Other names: Erbitux;Drug: Cisplatin<br>* Cisplatin total dose of >200 mg administered weekly (40 mg/m2/week) or every three weeks (100 mg/m2 every three weeks) according to local standard; not given in combination with cetuximab<br>* Other names: CDDP;Radiation: Radiotherapy<br>* 70 Gy / 5 fractions per week, over 7 weeks<br>* Other names: RTX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loss of body weight by more than 5% at the end of radiotherapy | Weekly body weight assessments - standardized method for all study sites | Difference between baseline and week 8 (after end of RTX) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioelectrical Impedance Analysis (BIA): reduction of phase angle by > 10% during treatment/observation | Determination of parameters on functional nutritional status: fat-free mass (FFM), total body water (TBW), body fat and phase angle will be evaluated by BIA | Prior to and 1 year after start of RTX, within 7 days and 3 months after end of RTX | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous Cell Carcinoma, Head and neck, SCCHN, Parenteral nutrition, Larynx, Hypopharynx, Cavum oris, Radiotherapy, Cetuximab, Cisplatin