Neoplasms

All Conditions

Symptoms and General Pathology

Head and Neck Neoplasms

Hypoxia

Signs and Symptoms, Respiratory

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

7 weeks Radiotherapy Intervention with with 5x2.3 Gy per week up to a total dose of 80.5 Gy and parallel chemotherapy of 20 mg/m²/d Cisplatin in week 1 and 5.

7 weeks Radiotherapy Intervention with 5x2.0 Gy per week up to a total dose of 70 Gy and parallel chemotherapy of 20 mg/m²/d Cisplatin in week 1 and 5.

7 weeks Radiation dose escalation (5 x 2.3 Gy up to 80.5 Gy total dose)

Radiotherapy

Sabine Barta, Dr.

Steffi U. Pigorsch, Dr. med.

Stephanie Combs, Prof. Dr.

The major clinical problem and predominant cause of death after radio-oncological treatment of H+N cancers are loco-regional relapses. This randomized trial tests the hypothesis that dose escalated Intensity Modulated Radiotherapy (IMRT) selectively applied to the macroscopic primary tumor and involved neck nodes - which both in 80% - are hypoxic improves loco-regional control by at least 15% at 2 years. IMRT is combined with concurrent Cis-Platin chemotherapy. Tumor volume which correlates with number of malignant cells as well as tumor hypoxia are important biological parameters which increase radio-resistance, failure of local control and tumor progression. Basing on data of experimental and clinical radiation oncology we consider hypoxia as a useful parameter for pre-therapeutic strati-fication in future randomized radio-chemotherapy trials.

In addition, hypoxia imaging by PET can be used for testing the significance of selective dose escalation on hypoxic tumor sub-volumes ("Dose Painting").

As a prerequisite for such innovative studies addressing hypoxia the translational part investigates the following key issues: correlation between the size of total tumor volume (primary, lymph nodes) and hypoxic sub-volume, the spatial shift of the hypoxic sub-volume before start of treatment and the correlation of loco-regional control and hypoxia.

Before starting the main study a pre-study to assess the occurrence of radiation induced toxicities is mandatory to be performed. In a step-wise dose-escalation in a cohort-design the safety of dose-escalation should be determined. Step one: 6 patients Step two: 14 patients. In the pre-study the 1st group (6 patients) should be treated with 2.2 Gy up to 77.0 Gy for DEVPT and DEVLK. After evaluation of the toxicity the next 14 patients should be treated by this scheme.

The pre-study with sequential design is a prospective multicentre interventional pilot study to assess toxicity of intensity modulated radiotherapy (IMRT) plus Cisplatin of head and neck cancers

The main study is a multicenter phase III randomized trial on the effect of dose escalated radiotherapy with concomitant chemotherapy to treat local advanced head and neck cancer. The study compares two treatment arms:

Experimental intervention (group A): 7 weeks standard radio-chemotherapy with 20 mg/m²/d Cisplatin in week 1 and 5 including simultaneous radiation dose escalation (5x2.3 Gy per week up to 80.5 Gy total dose) to the primary tumour and involved neck nodes ≥ 2 cm.

The Dose Escalated tumour Volume (DEVPT) is defined by the macroscopic (Gross) primary Tumour Volume (GTVPT) minus a 3 mm margin at organs at risk or at mucosal sites to reduce the risk of high dose deposition at the surrounding normal tissue. All involved lymph nodes visualized by CT with a minimal diameter of 2 cm are also included for dose escalation (DEVLN). The DEVLN of the lymph nodes \> 2 cm is determined by the involved lymph node volume (GTVLN) minus a margin of 3 mm at organs at risk or mucosal sites. The 3 mm margin as well as the part of the target volume with suspected microscopic tumor extension receives 2 Gy per fraction.

Control intervention (group B): 7 weeks standard radio-chemotherapy with 5x2.0 Gy per week up to a total dose of 70 Gy and 20 mg/m²/d Cisplatin in week 1 and 5.

In group A and B: The treatment of the elective cervical lymphatic areas is given in the same session as the GTV but with a single dose of 1.6 Gy up to 56 Gy (so called simultaneous integrated boost concept).

Impact of Selective Radiation Dose Escalation and Tumour Hypoxia Status on Locoregional Tumour Control After Radiochemotherapy of HNT

Phase III A Prospective, Randomized, Rater-blinded, Multicentre Interventional Clinical Trial. Do Selective Radiation Dose Escalation and Tumour Hypoxia Status Impact the Locoregional Tumour Control After Radiochemotherapy of Head & Neck Tumours?

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Impact of Selective Radiation Dose Escalation and Tumour Hypoxia Status on Locoregional Tumour Control After Radiochemotherapy of HNT	NCT01212354	Locally Advance...	Radiotherapy	18 Years - 70 Years	Technical University of Munich
Impact of Selective Radiation Dose Escalation and Tumour Hypoxia Status on Locoregional Tumour Control After Radiochemotherapy of HNT	NCT01212354	Locally Advance...	Radiotherapy	18 Years - 70 Years	Technical University of Munich

Spots Global Cancer Trial Database for selective dose escalation