Efficacy of Prophylactic Treatment With Antibiotics During Concomitant Chemoradiotherapy in Patients With Head and Neck Cancer to Prevent Aspiration Pneumonia (PANTAP)

Efficacy and Cost Efficacy of Prophylactic Treatment With Antibiotics During Concomitant Chemoradiotherapy in Patients With Locally Advanced Head and Neck Cancer to Prevent Aspiration Pneumonia. A Randomized Phase II-III Study

Patients with locally advanced head and neck cancer treated with chemo-radiotherapy have (during and shortly after this treatment) a high risk of developing pneumonia by aspiration. This pneumonia is often associated with a hospital admission and affects the quality of life.

The purpose of the study, is to determine whether prophylactic antibiotics may decrease the development of pneumonia. Prophylactic antibiotics means that there are no signs of pneumonia are already

Study Overview

• Status: Unknown
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: amoxicillin/clavulanic acid suspension

Detailed Description

Concomitant chemoradiotherapy (CRT) is used in locally advanced head and neck cancer (LAHNC). It will be administered to patients for unresectable disease or for organ preservation as primary treatment. Furthermore, it can be used as postoperative treatment in case high risk recurrent disease is present. This treatment induces a high rate of acute toxicity, such as mucositis, dermatitis, dysphagia, anorexia, and pain. Swallowing dysfunction and aspiration are seen in a high proportion (30%-100%) of patients and with an immense impact on Quality of life (QoL).

Around half of the patients will develop an aspiration pneumonia during or shortly after the treatment.

Patients, who develop fever during concomitant chemoradiotherapy, are most of the time admitted in the hospital. In the differential diagnosis pneumonia is on the first place in all those patients. The standard diagnostic procedures consist of a chest X-ray and culture of the sputum and blood. Pneumonia can lead to mortality in this frail patient group.

The treatment of patients treated with chemoradiotherapy who develop fever and have a definite or suspected pneumonia, is administration of antibiotics, most frequently intravenous amoxicillin/clavulanic acid.

LAHNC patients who are smoking and/or with malnutrition are at the highest risk of getting a pneumonia during or after radiotherapy. Because smoking is one of the risk factors of developing head and neck cancer chronic obstructive pulmonary disease (COPD) is frequently present in this group. Also, COPD is a known risk factor for developing pneumonias.

Aspiration is seen in all primary sites of head and neck cancer, sometimes it is seen more frequently in patients with cancer of the larynx and hypopharynx. No data of prophylactic administration of antibiotics are available in LAHNC patients. However, a Cochrane review was published to assess the effects of prophylactic antibiotic regimens for the prevention of respiratory tract infections(RTIs) and overall mortality in adults receiving intensive care.

• Study Type: Interventional
• Enrollment (Anticipated): 106
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: C. van Herpen, Md; Phone Number: +31 24 361 03 53; Email: c.vanherpen@onco.umcn.nl
• Study Contact Backup: Name: C. Driessen, drs; Phone Number: *pager: 3438 +31 24 361 11 11; Email: c.driessen@onco.umcn.nl

Study Locations

• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Not yet recruiting
    • Medisch Centrum Alkmaar
    • Contact: C. Smorenburg, Md; Phone Number: +31 72-5484444; Email: c.h.smorenburg@mca.nl
    • Contact: M. Komen; Phone Number: +31 72-5484444; Email: manon.komen@mca.nl
    • Principal Investigator: C. Smorenburg, Md
  • Groningen, Netherlands, 9700 RB
    • Recruiting
    • University Medical Centre Groningen
    • Contact: J. Gietema, Md; Phone Number: +31 50 361 61 61; Email: j.a.gietema@med.umcg.nl
    • Contact: G. Sieling; Phone Number: +31 50 361 61 61; Email: g.c.m.sieling@umcg.nl
    • Principal Investigator: J. Gietema, Md
  • Leeuwarden, Netherlands, 8934 AD
    • Not yet recruiting
    • Medisch Centrum Leeuwarden
    • Contact: E. Fiets, Md; Phone Number: +31 58-2866666; Email: edward.fiets@znb.nl
    • Contact: T. Rienks; Phone Number: +31 58-2866666; Email: tineke.rienks@znb.nl
    • Principal Investigator: E. Fiets, Md
  • Maastricht, Netherlands
    • Not yet recruiting
    • Academical Hospital Maastricht (AZM)
    • Contact: Email: ann.hoeben@mumc.nl
    • Principal Investigator: A. Hoeben, PhD
  • Gelderland
    • Arnhem, Gelderland, Netherlands, 6800 TA
      • Recruiting
      • Ziekenhuis Rijnstate
      • Contact: J. Blaisse, Md; Phone Number: +31 26-3788888; Email: jblaiss@alysis.nl
      • Contact: S. Brouwer; Phone Number: +31 26-3788888; Email: sbrouwer@rijnstate.nl
      • Principal Investigator: J. Blaisse, Md
    • Nijmegen, Gelderland, Netherlands, 6525 GH
      • Recruiting
      • University Medical Center Nijmegen st Radboud
      • Contact: C. van Herpen, Md; Phone Number: +31 24 361 03 53; Email: c.vanherpen@onco.umcn.nl
      • Contact: C. Driessen, drs; Phone Number: pager 3438 +31 24 361 11 11; Email: c.driessen@onco.umcn.nl
      • Sub-Investigator: C. Driessen, drs

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:

• Patients with LAHNC which will be treated with CRT as discussed by a multidisciplinary team (i.e. a head and neck surgeon, a medical oncologist, and a radiation oncologist). This can be CRT as primary treatment or postoperative CRT.
• Written informed consent
• Expected adequacy of follow-up

Exclusion Criteria:

• Patients with pneumonia within the last 14 days before start of CRT
• Patients with other infections within the last 14 days within the last 14 days before start of CRT
• Patients with use of maintenance antibiotics
• Patients with antibiotic treatment within the last 14 days before start of CRT
• Patients with an allergy on amoxicillin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: No prophylactic treatment; When a lower airway infection is suspected cultures will be taken and a chest radiography will be made; after that the standard care will be given (in most patients admission to hospital and start of intravenous antibiotics).
EXPERIMENTAL: prophylactic treatment; Administration of prophylactic amoxicillin/clavulanic acid suspension, 625 mg tid, start day 29 after the start of CRT until 14 days after the end of CRT. If a lower airway infection is suspected cultures will be taken and a chest radiography will be made; after that the standard care will be given (in most patients admission to hospital and start of intravenous antibiotics)	Drug: amoxicillin/clavulanic acid suspension; 625 mg tid, start day 29 after the start of CRT until 14 days after the end of CRT; Other Names: The total duration of the use of amoxicillin /clavulanic acid suspension will be between 20 and 27 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the number of definite pneumonia and/ or suspected pneumonia	Definite pneumonia: Evidence of pneumonia on chest radiography or 3 or more of the following: Sustained fever (temperature> 100 f [38°C]), Rales or rhonchi on chest auscultation Sputum Gram stain showing substantial leukocytes Sputum culture showing a respiratory pathogen Suspected pneumonia: At least 2 of the 4 following features are present, without evidence of pneumonia on chest radiography: Sustained fever (temperature> 100 f [38°C]) Rales or rhonchi on chest auscultation Sputum Gram stain showing substantial leukocytes Sputum culture showing a respiratory pathogen	from day 1 of 1 CRT until 3,5 mnd after the last CRT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effects on Quality of Life	to investigate the effects on QoL after prophylactic treatment with antibiotics Patients fill in the following questionnaires: QLQ-C30, EORTC H&N35, PSHHN, EQ-5D and the VAS, SF-36	Baseline, Day 28 last day of CRT, 3,5 months after CRT
Number and kind of positive blood cultures		from day 1 of 1 CRT until 3,5 mnd after the last CRT
number of admissions to hospital		from day 1 of 1 CRT until 3,5 mnd after the last CRT
Number of days of admission		from day 1 of 1 CRT until 3,5 mnd after the last CRT
Effects on mortality	Mortality due to definite and/or suspected pneumonia	from day 1 of 1 CRT until 3,5 mnd after the last CRT
effects on mucositis: grade and duration	Mucositis grade according to CTCAE v.4.0 and duration	from day 1 of 1 CRT until 3,5 mnd after the last CRT
side effects of amoxicillin/clavulanic acid	side effects of amoxicillin/clavulanic acid	from day 1 of 1 CRT until 3,5 mnd after the last CRT
Effects on numbers and causative agents of infections at other sites	numbers and causative agents of infections at other sites during follow up (3.5 months after the end of CRT)	during follow up

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: C. van Herpen, MD, University Medical Centre Nijmegen

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ANTICIPATED): December 1, 2013
• Study Completion (ANTICIPATED): December 1, 2014

Study Registration Dates

• First Submitted: February 2, 2012
• First Submitted That Met QC Criteria: May 14, 2012
• First Posted (ESTIMATE): May 15, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): July 15, 2013
• Last Update Submitted That Met QC Criteria: July 12, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: LAHNC; Locally Advanced Head and Neck Cancer
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Head and Neck Neoplasms; Pneumonia; Pneumonia, Aspiration; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Clavulanic Acid; Clavulanic Acids
• Other Study ID Numbers: UMCNONCO201007