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

Head and Neck Squamous Cell Carcinoma Clinical Trial

— DAHANCA30  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02661152
• Other study ID #: DAHANCA 30
• Status: Recruiting
• Phase: Phase 3
• Start date: September 2016
• Est. completion date: December 2023

Study information

• Verified date: April 2021
• Source: Danish Head and Neck Cancer Group
• Contact: Jens Overgaard, MD, DMSc
• Phone: +45 78462629
• Email: jens[@]oncology.au.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1252
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Gene Profile, Gene Signature
• Head and Neck Squamous Cell Carcinoma
• Hypoxia
• Hypoxic Modification
• Radiotherapy
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Nimorazole
Hypoxia gene profile is expected to discriminate between HNSCC responders and non-responders to hypoxic modification with nimorazole during radiotherapy. In DAHANCA 30 expected non-responders are randomized to +/- nimorazole during radiotherapy (non-inferiority study). Thus, similar efficacy of radiotherapy is expected in these groups. More hypoxic tumours receive nimorazole after DAHANCA standards.

Locations

Country	Name	City	State
Denmark	Department of Experimental Clinical Oncology, Aarhus University Hospital	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
Danish Head and Neck Cancer Group

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with locoregional tumour control	Patients are being followed with regular clinical examinations for 5 years after therapy. Side effects, tumour control and survival status is registered in the DAHANCA database. Interim analysis are planned every 12 months.	5 years
Secondary	Number of participants with disease specific survival	Patients are being followed with regular clinical examinations for 5 years after therapy. Side effects, tumour control and survival status is registered in the DAHANCA database. Interim analysis are planned every 12 months.	5 years