IAEA-HypoX. Accelerated Radiotherapy With or Without Nimorazole in Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that radiotherapy of head and neck carcinoma can be improved by hypoxic modification of radiotherapy using nimorazole as a hypoxic radiosensitizer in association with accelerated fractionation, in an unselected patient population in a global environment.

Detailed Description
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Squamous cell carcinoma in the head & neck region (HNSCC) accounts for approximately 7% of all cancers worldwide & around 75% of all HNSCC cases are seen in the less developed countries. Significant improvement in loco-regional control & disease specific survival by radiation therapy could be achieved by reducing the overall treatment time by Accelerated Fractionation schedule. Modification of hypoxia by Nimorazole demonstrated significant improved local effect of radiation with neither serious nor lasting side effects. So, it is expected that the optimal treatment option is reducing the overall treatment time with concomitant use of Nimorazole. Such treatment principle is optimal for testing in developing countries. The aim of the study: To determine the possible therapeutic gain of using nimorazole given as a hypoxic radiosensitizer in conjunction with accelerated fractionated radiotherapy of invasive squamous cell carcinoma of the larynx, pharynx and oral cavity, and To determine whether the addition of Nimorazole to primary curative radiotherapy is feasible and tolerable on a worldwide scale. To evaluate the tolerance, compliance and toxicity of using nimorazole.

Official Title
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IAEA-HypoX. A Randomized Multicenter Study of Accelerated Fractionated Radiotherapy With or Without the Hypoxic Radiosensitizer Nimorazole in the Treatment of Squamous Cell Carcinoma of the Head and Neck

Conditions
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Head and Neck Carcinoma

Intervention / Treatment
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* Radiation: Accl. RT
* Radiation: Accl. radiotherapy + Nimorazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Tumor classified as stage I-IV located in oropharynx, hypopharynx, larynx (not glottic stage I-II), or oral cavity according to the TNM classification. Histopathological diagnosis of invasive squamous cell carcinoma in the primary tumor. Informed consent according to the Helsinki declaration and local regula-tions. The patient must be candidate for external beam radical radiotherapy, and must be expected to accomplish the treatment. Performance status 0-2 according to WHO criteria. The patient should not have symptoms of peripheral neuropathy assessed by clinical examination. Normal function of liver and kidney by routine laboratory examinations. The patient must not be pregnant Exclusion Criteria: Distant metastases. The patient should not be in a state or condition that could be expected to influence the outcome of treatment, or complicate the assessment or the treatment follow-up, or (apart from the present disease) reduce the life expectancy. Surgical excision (except biopsy), prior or planned (including elective neck dissection). The existence of synchronous multiple malignancies (not leukoplakia).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Accl. RT<br>Accelerated Radiotherapy 66-70 Gy, 2Gy/fx, 6fx/week | Radiation: Accl. RT<br>* Accelerated Radiotherapy: Radiotherapy 66-70 Gy, 2Gy/fx, 6fx/week<br>* Other names: Radiation Oncology, Accelerated fractionation;|
| Experimental: Accl. RT + Nimorazole<br>Accelerated Radiotherapy 66-70 Gy, 2Gy/fx, 6fx/week + Nimorazole | Radiation: Accl. RT<br>* Accelerated Radiotherapy: Radiotherapy 66-70 Gy, 2Gy/fx, 6fx/week<br>* Other names: Radiation Oncology, Accelerated fractionation;Radiation: Accl. radiotherapy + Nimorazole<br>* Radiation: Radiotherapy 66-70 Gy, 2Gy/fx, 6fx/week plus Nimorazole (tablets or powder) 1.2 g/m2 body surface in connection with the first daily radiation treatments<br>* Other names: Hypoxic radiosensitizer, Nimorazole, Nimoral;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Locoregional control after curative intended radiotherapy +/- Nimorazole |  | 5-years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease specific survival |  | 5.years | 
| Overall survival |  | 5-years | 
| Treatment related morbidity | Treatment related acute and late morbidity releted to radiotherapy and/or nimorazole treatment | 5-years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and neck carcinoma, Accelerated radiotherapy, Hypoxic modification with Nimorazole