Study on Proton Radiotherapy of Thymic Malignancies

Study Overview
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Brief Summary
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This is a multicentre non-randomized phase II study of proton beam radiotherapy in patients with thymic epithelial tumours (i.e. thymoma and thymic carcinoma) in the post-operative setting or in inoperable patients with localized disease. Patients not willing or for any reason unsuitable to undergo proton treatment will be asked to participate in a follow-up assessment after the regular photon treatment in the same manner as the included patients. Primary endpoints are:Toxicity (e.g. cardiac and pulmonary toxicity) and Local control at 5 year Secondary endpoints: PFS, Overall survival, Quality of life, measured by EORTC QLQ 30 + LC 13 and relapse pattern

Detailed Description
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All doses are recorded in Gy(RBE). After having checked all eligibility criteria patients will receive: Patients with radical surgery and unfavourable histology (B2, B3, C) and/or Masaoka-Koga stage III, IVa: 2 Gy(RBE), once daily, five days a week to a total dose of 50 Gy(RBE). Patients with non-radical surgery (R1 resection) regardless of stage and histology: 2.3 Gy(RBE), once daily, 5 days a week to a total dose of 57.5 Gy(RBE) Inoperable patients regardless of stage and histology and patients with R2 non-radical resection: 2.5 Gy (RBE), once daily, 5 days a week to a total dose of 62.5 Gy(RBE) Patients not willing to participate in study will receive photon therapy according to local practice (≥45 Gy) Induction or adjuvant chemotherapy may be used according to local practice. Concomitant chemotherapy is not allowed.

Official Title
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PROTHYM - Phase II Non-randomized Study on Proton Radiotherapy Of Thymic Malignancies

Conditions
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Pulmonary Toxicity, Cardiotoxicity, Thymus Neoplasms

Intervention / Treatment
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* Radiation: Proton radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological diagnosis of thymoma or thymic carcinoma. With radical surgery: stage III and IVa and selected stage II with type B2, B3 and thymic carcinoma according to local routine. With non-radical surgery (R1 or R2) or inoperable patient/ patient refusing surgery: stage I - IVa, any histology PS WHO 0 - 2. FEV1 > 1L or >40 % of predicted and CO diffusion capacity > 40% of predicted (postoperative measures) Age >18 years, no upper age limit. Written informed consent from patients. Exclusion Criteria: Masaoka-Koga stage IVb (distant metastases). Pregnancy. Serious concomitant systemic disorder incompatible with the study. Tumour motion > 0.5 cm on two repeated 4DCT

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
Intervention Model: Single Group Assignment
Interventional Model Description: Phase II study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proton radiotherapy<br>Proton radiotherapy with RBE doses: Patients with radical surgery and unfavourable histology (B2, B3, C) and/or Masaoka-Koga stage III, IVa: 2 Gy(RBE), once daily, five days a week to a total dose of 50 Gy(RBE). Patients with non-radical surgery (R1 resection) regardless of stage and histology: 2.3 Gy(RBE), once daily, 5 days a week to a total dose of 57.5 Gy(RBE) Inoperable patients regardless of stage and histology and patients with R2 non-radical resection: 2.5 Gy (RBE), once daily, 5 days a week to a total dose of 62.5 Gy(RBE) | Radiation: Proton radiation<br>* Patients with radical surgery and unfavourable histology (B2, B3, C) and/or Masaoka-Koga stage III, IVa: 2 Gy(RBE), once daily, five days a week to a total dose of 50 Gy(RBE). Patients with non-radical surgery (R1 resection) regardless of stage and histology: 2.3 Gy(RBE), once daily, 5 days a week to a total dose of 57.5 Gy(RBE) Inoperable patients regardless of stage and histology and patients with R2 non-radical resection: 2.5 Gy (RBE), once daily, 5 days a week to a total dose of 62.5 Gy(RBE)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiotoxicity and pulmonary toxicity of therapy | Proportion of patients with cardiac and pulmonary toxicity measured by CTCAE 4.0 > Grade 2 | At 60 months from treatment | 
| Local tumor control | Freedom from tumor progression (CR,PR or SD) mesured by CT-scan | At 60 months from treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life questionnaire EORTC QLQ 30 (European Organisation for Research and Treatment of Cancer) | Scale from 1-100 for 30 items, higher score indicates a better situation. | At 60 months from treatment | 
| Quality of life questionnaire LC13 (Lung cancer specific module of EORTC) | Scale from 1-100 for 13 items and higher score indicates worse symptoms. | At 60 months from treatment | 
| Survival | Overall survival | From treatment and for 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thymoma, Thymic carcinoma, Proton radiotherapy