Comparing Two Palliative Schemes of Radiotherapy for Head and Neck Cancer

Study Overview
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Brief Summary
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RCT to compare two radiation schemes for palliative HeadNeck cancer

Detailed Description
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A substantial proportion of patients with head and neck (HNC) are not suitable for curative treatment with surgery and/or (chemo)radiotherapy (CRT) because of very advanced stage, significant comorbidities, bad general condition, distant metastasis, or a combination of these factors. Although radiotherapy (RT) is a commonly used option to achieve durable disease control and to alleviate troublesome symptoms, the data about the optimal radiation scheme and the impact of these schedules on quality of life (QoL) of these vulnerable patients is extremely scarce. Although different radiation schemes are used worldwide (in the Netherlands, at least 15 different radiation schedules are used), it is currently not possible to identify the best RT scheme, based only on retrospective studies because of the major differences between these studies with regard to patient's demographics, radiation schedules given, the radiation technique used etc. Furthermore, no any information is available on the impact of these schemes on treatment-related toxicity and QoL. This illustrates the urgent need for a multicenter randomized controlled trial (RCT) to identify the most optimal schemes of RT for this group of patients. Therefore, the investigators intend to initiate a prospective RCT comparing the survival, loco-regional control, toxicity, and QoL of two commonly used schemes. This study will be the first of his kind for palliative patients with HNC and will compare a short-course (6 fractions) with a long-course of radiotherapy (16 fractions). Because most of patients with incurable HNC have a poor performance status and major comorbidity and prefer limited number of visits to the hospital, it is quite reasonable to investigate whether a short scheme of radiotherapy with limited number of visits to the clinic as good as a relatively long-course of radiotherapy in terms of outcome, toxicity and QoL. This delicate balance between outcomes, possible toxicity and patient's comfort would justify the initiation of such randomized trial. The results of this study will in the nearby future enable us to indicate the radiation scheme best suits which patient category

Official Title
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Dutch Randomized Multicenter Trial COmparing twO PalliativE RAdiaTION Schemes for Incurable Head and Neck Cancer (COOPERATION)

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Radiation: 6 x 6 Gy
* Radiation: 16 x 3.125 Gy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Newly diagnosed patients with primary non-metastatic carcinoma located in the oral cavity, oropharynx, larynx (except T1 glottic), hypopharynx, nasopharynx, paranasal sinuses and salivary gland and carcinoma of unknown primary in the head and neck region who are not suitable for radical treatment with surgery or (chemo) and, therefore, planned for treatment with radiotherapy in palliative setting. OR Newly diagnosed patients with primary head and neck carcinoma with limited metastatic disease in a good general condition and few comorbidities (ACE-25 <3) with life expectancy of at least 6 months are also eligible. No chemotherapy or surgery is allowed before inclusion. Age ≥ 18 years WHO performance status 0-2 Signed written informed consent Exclusion Criteria: Patients with previously radiation treatment in the head and neck region, for any reason. * Chemotherapy or surgery for head and neck tumor before inclusion and no other concomitant anti-cancer therapy is allowed during study treatment. Patients with head and neck malignancies arising from skin, nose, thyroid gland or esophagus. Patients with advanced stage sarcoma or lymphoma of the head and neck region. Expected life expectancy of less than 3 months

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: arm 1: 6 fractions of radiation<br>radiation in a 6 fractions scheme and a daily dose of 6 Gy | Radiation: 6 x 6 Gy<br>* radiation in 6 fraction of 6 Gy, twice a week during 3 weeks<br>|
| Active Comparator: arm 2: 16 fractrions of radiation<br>radiation in a 16 fractions scheme and a daily dose of 3.125 Gy | Radiation: 16 x 3.125 Gy<br>* radiation in 16 fraction of 3.125 Gy, 4 times a week during 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to loco-regional progression | caculated from date of response until the date of clinical deteriotion; accoriding to RECIST | 4 months | 
| impact of both radiation schemes on QoL | this will be measured by the EORTC questionnaires C30 and HN35; analysis will be performed by a random effects regression model | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival rates | RECIST | 4 months | 
| loco-regional control rates | caculated from date of response until the date of clinical deteriotion; according to RECIST | 3 months | 
| overall response rates | caculated from date of response until the date of clinical deteriotion; accoriding to RECIST | 2 year | 
| compliance to the study treatments as assessed by completed treatment and follow-up visits | number of treatment fractions and follow-up visits | 4 months | 
| the incidence of grade ≥ 2 acute and late toxicity | scoring of AE according tot CTC 4.0 | 2 years |