DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification of Radiotherapy of HNSCC. (DAHANCA30)

Danish Head and Neck Cancer Group

Status and phase: Unknown; Phase 3

Conditions: Hypoxic Modification; Radiotherapy; Gene Profile, Gene Signature; Hypoxia; Head and Neck Squamous Cell Carcinoma

Treatments: Drug: Nimorazole

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT02661152

DAHANCA 30

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,252 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

1,252 participants in 2 patient groups

Radio-/Chemoradiotherapy + nimorazole

Experimental group

Description:

Hypoxia profile guided non-responder (less hypoxic tumour) to nimorazole but receiving the drug, which is normal standard radiotherapy of HNSCC in Denmark.

Treatment:

Drug: Nimorazole

Radio-/Chemoradiotherapy

No Intervention group

Description:

Hypoxia profile guided non-responder (less hypoxic tumour) to nimorazole and not receiving the drug, that is normally part of standard radiotherapy of HNSCC in Denmark.