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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Radboud University
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01598402
First received: February 2, 2012
Last updated: July 12, 2013
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Head and Neck Cancer
Drug: amoxicillin/clavulanic acid suspension
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • the number of definite pneumonia and/ or suspected pneumonia [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]

    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



Secondary Outcome Measures:
  • effects on Quality of Life [ Time Frame: Baseline, Day 28 last day of CRT, 3,5 months after CRT ] [ Designated as safety issue: No ]

    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


  • Number and kind of positive blood cultures [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]
  • number of admissions to hospital [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]
  • Number of days of admission [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]
  • Effects on mortality [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]
    Mortality due to definite and/or suspected pneumonia

  • effects on mucositis: grade and duration [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]
    Mucositis grade according to CTCAE v.4.0 and duration

  • side effects of amoxicillin/clavulanic acid [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]
    side effects of amoxicillin/clavulanic acid

  • Effects on numbers and causative agents of infections at other sites [ Time Frame: during follow up ] [ Designated as safety issue: No ]
    numbers and causative agents of infections at other sites during follow up (3.5 months after the end of CRT)


Estimated Enrollment: 106
Study Start Date: December 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: The total duration of the use of amoxicillin /clavulanic acid suspension will be between 20 and 27 days.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01598402

Contacts
Contact: C. van Herpen, Md +31 24 361 03 53 c.vanherpen@onco.umcn.nl
Contact: C. Driessen, drs +31 24 361 11 11 ext *pager: 3438 c.driessen@onco.umcn.nl

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

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01598402     History of Changes
Other Study ID Numbers: UMCNONCO201007
Study First Received: February 2, 2012
Last Updated: July 12, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
LAHNC
Locally Advanced Head and Neck Cancer

Additional relevant MeSH terms:
Pneumonia, Aspiration
Head and Neck Neoplasms
Pneumonia
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Amoxicillin
Anti-Bacterial Agents
Clavulanic Acids
Clavulanic Acid
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014