Carbon Ion Re-Radiotherapy in Patients With Recurrent or Progressive Locally Advanced Head-and-Neck Cancer

Study Overview
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Brief Summary
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After multimodal therapy of head-and-neck tumors, patients often develop local recurrence, locally progressive disease or second primary tumors. In this highly pre-treated patient cohort, therapeutic options are limited. Patients that are not candidates for salvage surgery may benefit from re-irradiation. Despite recent technical advances, re-irradiation is associated with severe side effects. Carbon ion Re-Radiotherapy (reCIRT) has shown encouraging results in retrospective analyses with moderate toxicity. In the current Phase-II CARE-trial, reCIRT and conventional photon re-irradiation in patients with recurrent or progressive locally advanced head-and-neck cancer will be assessed regarding toxicity/ safety, local progression-free survival, overall survival and quality-of-life.

Detailed Description
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The incidence of head-and-neck cancer worldwide amounts to around 550.000 cases per year, with male patients affected significantly more often. Common risk factors are smoking, alcohol, viral infections, immunodeficiency or genetic factors. Locally advanced head-and-neck tumors can lead to severe symptoms such as dysphagia, cachexia and tumor pain with a significant decrease of the quality-of-life. The prognosis depends on multiple factors such as TNM-staging, tumor volume, histology, general condition, age and smoking. Further risk factors are positive resection margins, extracapsular extension and perineural invasion. While metastatic spread significantly decreases overall survival, the life-limiting problem in patients with head-and-neck cancer is locally invasive and destructive tumor growth leading to a decrease of the performance status and quality of life. After multimodal therapy of locally advanced head-and-neck tumors, around 30 - 50% of patients will develop local recurrence or locally progressive disease and up to 8% of patients with HNSCC will develop a second primary tumor in the head-and-neck .

Official Title
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Carbon Ion Re-Radiotherapy in Patients With Recurrent or Progressive Locally Advanced Head-and-Neck Cancer: A Phase-II Study to Evaluate Toxicity and Efficacy

Conditions
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Locally Advanced Head-and-Neck Cancer

Intervention / Treatment
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* Radiation: C12 re-irradiation
* Radiation: Photon re-irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally recurrent / progressive head-and-neck cancer after initial radiation therapy Microscopic or macroscopic tumor after salvage surgery Indication for re-irradiation Completed wound healing after surgical intervention Karnofsky-Performance-Score ≥ 60 Age ≥ 18 years Written informed consent (must be available before enrolment in the trial) Ability of subject to understand character and individual consequences of the trial For women with childbearing potential, (and men) adequate contraception Submission of previous radiotherapy records Exclusion Criteria: Re-irradiation of malignancy in the larynx Diagnosed plasmocytoma, sarcoma or chordoma Previous re-irradiation in-field Time interval < 6 months after initial radiotherapy Distant metastases (except pulmonary metastases) Patients who have not recovered from acute toxicities of prior therapies Refusal of the patients to take part in the study Pregnant or lactating women Known carcinoma <5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy Participation in another clinical study or observation period of competing trials, respectively

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
Interventional Model Description: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C12 irradiation<br>Evaluation of Safety and Toxicity of C12 ion reirradiation | Radiation: C12 re-irradiation<br>* 51 Gy(RBE) or 54 Gy<br>|
| Active Comparator: Photon irradiation<br>Evaluation of Safety and Toxicity of photon re-irradiation | Radiation: Photon re-irradiation<br>* 54 Gy(RBE) or 60 Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety of carbon ion re-irradiation | the rate of patients with an acute/subacute toxicity CTCAE v5.0 ≥ grade 3 | 6 month | 
| toxicity of carbon ion re-irradiation | the rate of patients with an acute/subacute toxicity CTCAE v5.0 ≥ grade 3 | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival | Local progression-free survival | 12 month | 
| Overall survival | within 12 month after re-irradiation | 12 month | 
| Score on EORTC QLQ C30 Quality of life questionaire | EORTC (European Organization for Research and. Treatment of Cancer) QLQ (quality of life questionnaire) C30, score 1-6, high score means worse outcome | within 12 month after re-irradiation | 
| Score on EORTC QLQ H&N35 Quality of life questionaire | QLQ (quality of life questionnaire)-H&N (Head and neck) 35, score 1-6, high score means worse outcome | within 12 month after re-irradiation |