Hypoxia Analysis in Head and/or Neck Cancer

Predictive Methods Determining Tumour Hypoxia in Head and Neck Cancer Patients - a Prospective Project

The primary objective is the prospective determination of disease-specific and overall survival in head and neck cancer patients who have undergone surgery, correlated to non-invasive methods of measuring tumour hypoxia.

The secondary objective is to define tumour hypoxia using non-invasive methodology.

Study Overview

• Status: Unknown
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Pimonidazole

Detailed Description

The incidence of head and neck squamous cell cancer (HNSCC) is around 600 000 cases per year worldwide. The main sites for HNSCC are the larynx, the pharynx and the oral cavity. Head and neck cancers, however, also include salivary gland tumours, as well as nasopharyngeal cancer and paranasal and nasal sinus cancer but these are rare. The major risk factors are smoking, alcohol abuse and Human Papillomavirus (HPV) infection. In spite of radical surgical treatment and aggressive neo-adjuvant and adjuvant therapies, the prognosis of head and neck cancer is very poor due to the fact that the tumours are often hypoxic.

Tumour hypoxia is heterogenous and results from an imbalance between oxygen supply and oxygen consumption. Acute hypoxia is caused by abnormal structure and function of the microvasculature supplying the tumour. Chronic hypoxia is caused by the increased distance through which the oxygen has to diffuse to get from the blood vessels to the tumour cells and by the reduced oxygen caused by the anaemia which can be treatment or disease-related. These hypoxic regions have been shown to affect the metabolism of the cells, making them more aggressive with increased risk of metastasis and a worse prognosis. Also, because radiotherapy relies on oxygen to cause maximal cytotoxicity, a lack of oxygen to the cells or even a lack of oxygen consumption by the cells would cause a decrease in the effectiveness of the radiotherapy and the cytotoxicity. Hypoxic cells have an acidic environment which affects drug delivery and drug activity, so chemotherapy is compromised.

In order to predict outcome and identify patients with a worse prognosis or patients that would benefit from appropriate treatments, in vivo measurement of tumour hypoxia is required. Numerous methods have been explored but there is no accepted gold standard. Imaging and biomarker analysis have been shown to have potential but the data are insufficient. In this project the investigators would prospectively use existing imaging techniques and analysis of various bodily fluids to predict outcome. This is a collaboration between 5 different departments so that as much information as possible can be analysed and used to come to a possible solution.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christine Hager; Email: christine.hager@usz.ch

Study Locations

• Switzerland
  • Zürich, Switzerland, 8090
    • Recruiting
    • Department of Cranio-, Maxillofacial and Oral Surgery
    • Contact: Christine Hager; Email: christine.hager@usz.ch

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:

• Malignancy in head and/or neck region only
• Interdisciplinary Head and neck tumour board (USZ) confirmed inclusion in the project
• For patients with reproductive potential (e.g. female participants who are surgically sterilised/hysterectomised or post-menopausal for longer than 2 years are not considered as beig of child bearing potential), a willingness to use adequate contraceptive measures to prevent pregnancy during the project.

Exclusion Criteria:

• Pregnant or breastfeeding
• Suffers from claustrophobia
• Known allergy to Pimonidazole
• Participation in a study with an investigational drug within the 30 days preceding and during this project
• Tumour size smaller than 1cm
• Has symptomatic Chronic Obstructive Pulmonary Disease (COPD)
• Patient refuses or is unable to give a written informed consent
• Previous treatment for head and/or neck cancer
• Inability to follow the procedures of the project e.g. due to language problems, psychological disorders, dementia, etc. of the participant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pimonidazole; All patients will receive Pimonidazole to demarcate hypoxia regions in the tumour	Drug: Pimonidazole; Pimonidazole will be administered orally and will serve to demarcate the hypoxic areas in the tumour; Other Names: Oral Hypoxyprobe

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-specific and overall survival correlated with tumour hypoxia	Tumour hypoxia will be determined from the Pimonidazole staining and this will be correlated to disease-specific survival and overall survival. The study has been approved for 10 participants to be increased by the ethical committee to 100 once the study is going.	5-years

Collaborators and Investigators

• Sponsor: Marius Gustav Bredell
• Investigators: Principal Investigator: Marius Bredell, Department of Cranio-, Maxillofacial and Oral Surgery, University Hospital Zurich

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: April 7, 2015
• First Submitted That Met QC Criteria: April 9, 2015
• First Posted (Estimate): April 10, 2015

Study Record Updates

• Last Update Posted (Estimate): June 17, 2016
• Last Update Submitted That Met QC Criteria: June 16, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Hypoxia; Head and neck cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Signs and Symptoms, Respiratory; Head and Neck Neoplasms; Hypoxia
• Other Study ID Numbers: KEK-Nr.2014-0393