Randomized Carbon Ions vs Standard Radiotherapy for Radioresistant Tumors

Study Overview
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Brief Summary
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This is a transnational prospective randomized trial comparing definitive carbon ion therapy versus photon or combined photon and protontherapy as standard treatment for unresectable or macroscopically uncompleted resected radioresistant tumors. Eligible tumors are axial chordoma (except of base of skull), adenoid cystic carcinoma of head and neck (except of trachea) and sarcomas of any site (except chondrosarcoma of the skull base), non previously irradiated and without pre-planned surgery or chemotherapy after the clinical trial procedure. Randomization is balanced 1 for 1. Patients of the experimental arm are treated in carbon ions centers in Europe and patients of the standard arm are treated in France in their closest participating radiotherapy center. An accrual of 250 patients is needed and an absolute difference of 20% of relapse free survival at five years is awaited. The main endpoint is the progression free survival at five years. The trial is supported by the French program of clinical research and the national health insurance. Two associated studies are carried out: a radiobiological one looking for radioresistance markers in the sarcomas biopsies, and the second one is about medico economics.

Official Title
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Transnational Randomized Study Comparing Carbon Ions Therapy Versus Conventional Radiotherapy - Including Protontherapy - for the Treatment of Radioresistant Tumors

Conditions
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Malignant Tumors as Chordoma, Adenoid Cystic Carcinoma and Sarcoma

Intervention / Treatment
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* Radiation: Carbon ions therapy
* Radiation: Advanced external radiotherapy by Xrays or protons


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 years No severe comorbidity, life expectancy above 10 years Unresectable or inoperable or R2 resection of the tumor Eligible radioresistant tumor according to the limitative list as following: adenoid cystic carcinoma of head and neck (larynx and trachea excluded) soft tissue sarcoma pleomorphic rhabdomyosarcoma only (alveolar and embryonal forms excluded) retroperitoneal sarcoma under condition of technical feasibility (movement) osteosarcoma of any grade and localisation (Ewing excluded) chondrosarcoma (except of skull base) OMS grade >= 2 chordoma axial skeleton or pelvis (except of skull base) angiosarcoma Absence of epidermal invasion (a hypodermic invasion is accepted with fixity of cutaneous plan but not true epidermal permeation) Larger volume to be irradiated (PTV) less than 25 cm ECOG Performance Status ≤ 2 or Karnovsky index ≥ 60 no pregnancy of possibility of pregnancy during the treatment having an health insurance signature of a written informed consent validation of the randomization criteria: namely, a carbon ions therapy indication assessed by the medical team of a hadrontherapy center and able to by treated within two month from registration. Exclusion Criteria: Complete macroscopic or microscopic surgical resection (R0 or R1) previous irradiation in the volume to be treated metastatic disease disease not candidate to a curative approach (example accelerated progressive diseaseresistant to nay medical treatment especially for sarcoma) any contra-indication to undergo a radiation therapy by Xray or particle therapy planned surgery or chemotherapy to take place after completion of radiotherapy (example : absence of enough space between an organ risk and the target volume (at least 5 mm) except the possibility of a spacer insertion) planned surgery or chemotherapy after radiotherapy Presence in the target volume of metallic material which cannot be removed (carbon fibres matreial authorized) history of concomittant (except in situ cervix carcinoma; or any cured basocellular cutaneous cancer tor any cured cancer with no sign of relapse during 5 years)) impossible follow-up over 5 years

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 |
| --- | --- |
| Experimental: Carbon ions therapy<br>Radical and exclusive carbon ions radiotherapy | Radiation: Carbon ions therapy<br>* External radiotherapy by accelerated carbon nucleus in a specialized hadrontherapy center<br>|
| Active Comparator: Conventional radiotherapy<br>Radical radiotherapy by Xrays and / or protons | Radiation: Advanced external radiotherapy by Xrays or protons<br>* Radiotherapy by any appropriate advance procedure of photontherapy (IMRT, Volumetric Modulated Arc Therapy (VMAT), Tomo, etc.) or when possible by protontherapy or even a combination of both types of radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | Starting point for PFS measurement is the randomization date | up to 5 years or loss of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grades of the CTCAE-V4.02 classification | Tolerance | up to 5 years or loss of follow-up | 
| EQ-5D questionnaire | Quality of life | up to 5 years or loss of follow-up | 
| Local progression free survival | takes account of the local progression of the tumor in the planning target volume (PTV) | up to 5 years or loss of follow-up | 
| Metastases free survival | takes account of any site of relapse outside of the PTV | up to 5 years or loss of follow-up | 
| Overall survival | delay of death of any cause accounted starting from randomization | up to 5 years or loss of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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carbon ions therapy, radiotherapy, radioresistant tumors, cancer, randomized trial