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

Head and Neck Cancer Clinical Trial

— PANTAP  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01598402
• Other study ID #: UMCNONCO201007
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: February 2, 2012
• Last updated: July 12, 2013
• Start date: December 2011
• Est. completion date: December 2014

Study information

• Verified date: July 2013
• Source: Radboud University
• Contact: C. van Herpen, Md
• Phone: +31 24 361 03 53
• Email: c.vanherpen[@]onco.umcn.nl
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: December 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Pneumonia, Aspiration

Intervention

Drug:
• amoxicillin/clavulanic acid suspension
625 mg tid, start day 29 after the start of CRT until 14 days after the end of CRT

Locations

Country	Name	City	State
Netherlands	Medisch Centrum Alkmaar	Alkmaar
Netherlands	Ziekenhuis Rijnstate	Arnhem	Gelderland
Netherlands	University Medical Centre Groningen	Groningen
Netherlands	Medisch centrum Leeuwarden	Leeuwarden
Netherlands	Academical Hospital Maastricht (AZM)	Maastricht
Netherlands	University Medical Center Nijmegen st Radboud	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Number and kind of positive blood cultures		from day 1 of 1 CRT until 3,5 mnd after the last CRT	No
Secondary	number of admissions to hospital		from day 1 of 1 CRT until 3,5 mnd after the last CRT	No
Secondary	Number of days of admission		from day 1 of 1 CRT until 3,5 mnd after the last CRT	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No