Clinical trial NCT02661152: DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification of Radiotherapy of HNSCC.
Official title: DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification With Nimorazole During Radiotherapy/Chemoradiotherapy of Squamous Cell Carcinoma of the Head and Neck.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma
Radiotherapy
Hypoxic Modification
Hypoxia
Gene Profile, Gene Signature
Lead sponsor: Danish Head and Neck Cancer Group
Sponsor class: NETWORK
First posted: 2016-01-22
Enrollment: 1252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Hypoxic modification of radiotherapy with nimorazole has previously been shown to increase radiosensitivity in hypoxic head and neck squamous cell carcinomas (HNSCC).

In Denmark, nimorazole is added the radiotherapy of most HNSCC, as it has not previously been possible to discriminate more hypoxic tumours from less hypoxic tumours.

A hypoxia gene profile has shown to discriminate between responders and non-responders to nimorazole.

In DAHANCA 30, expected hypoxia profile guided non-responders are randomized to +/- nimorazole during radiotherapy.This in order to verify clinical use of the gene profile in selecting the relevant patients for hypoxic modification of radiotherapy with nimorazole.

Detailed description: Hypoxic modification of radiotherapy with nimorazole has in the DAHANCA 5 trial been shown to increase radiosensitivity in hypoxic head and neck squamous cell carcinomas (HNSCC).

Previously, it has not been possible to discriminate more hypoxic tumours from less hypoxic tumours. Thus, nimorazole has been added the radiotherapy of most HNSCC.

Recently, a hypoxia gene profile has been developed, that discriminate between more and less hypoxic tumours. The basis of the discrimination is the cumulated expression of 15 hypoxia responsive genes, quantified from the tumour biopsy.

The profile has been validated on the independent DAHANCA 5 cohort. There was a significant effect of adding nimorazole to the radiotherapy of more hypoxic tumours as estimated with the gene profile, whereas there was no effect of adding nimorazole to the less hypoxic tumours. In a test for interaction, there was a significantly different response to nimorazole in the more hypoxic tumours compared to the less hypoxic tumours.

In the Dahanca 30 trial it is aimed to verify, that there is no benefit of supplying the radiotherapy of less hypoxic HNSCC with nimorazole. Thus, to explore whether it is possible to avoid the sideeffects of nimorazole without risk for the patient.

Eligibility criteria: Inclusion Criteria:

* Head and neck squamous cell carcinoma with indication for hypoxic modification with nimorazole in accordance to the Danish Head and Neck Cancer guidelines (DAHANCA guidelines).
* Informed consent

Exclusion Criteria:

* Previous or present malignant disease conflicting with the radiotherapy treatment or evaluation of the treatment.
* Participation in a conflicting protocol.
* Initiation of radiotherapy more than 3 weeks after inclusion

Primary outcomes:
measure: Number of participants with locoregional tumour control
timeFrame: 5 years
Secondary outcomes:
measure: Number of participants with disease specific survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Experimental Clinical Oncology, Aarhus University Hospital
Study officials:
affiliation: DAHANCA Danish Head and Neck Group
name: Jens Overgaard, MD DMSc
role: STUDY_CHAIR
References: