Clinical trial NCT02838602: Randomized Carbon Ions vs Standard Radiotherapy for Radioresistant Tumors
Official title: Transnational Randomized Study Comparing Carbon Ions Therapy Versus Conventional Radiotherapy - Including Protontherapy - for the Treatment of Radioresistant Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Malignant Tumors as Chordoma, Adenoid Cystic Carcinoma and Sarcoma
Keywords: carbon ions therapy
radiotherapy
radioresistant tumors
cancer
randomized trial
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2016-07-20
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: up to 5 years or loss of follow-up
Secondary outcomes:
measure: Grades of the CTCAE-V4.02 classification
timeFrame: up to 5 years or loss of follow-up
measure: EQ-5D questionnaire
timeFrame: up to 5 years or loss of follow-up
measure: Local progression free survival
timeFrame: up to 5 years or loss of follow-up
measure: Metastases free survival
timeFrame: up to 5 years or loss of follow-up
measure: Overall survival
timeFrame: up to 5 years or loss of follow-up
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens - Hôpital Sud
city: Caen
country: France
facility: Radiothérapie, CLCC François Baclesse
city: Clermont-Ferrand
country: France
facility: Radiothérapie, CRLCC Jean Perrin
city: Dijon
country: France
facility: Radiothérapie, CRLCC GF Leclerc
city: Grenoble
country: France
facility: Radiothérapie, Hôpital A. Michallon, CHU de Grenoble
city: Lille
country: France
facility: Radiothérapie, CRLCC Oscar Lambret
city: Lyon
country: France
facility: Radiothérapie, CRLCC Léon Bérard
city: Marseille
country: France
facility: Radiothérapie, CRLCC Institut Paoli Calmettes
city: Montpellier
country: France
facility: Radiothérapie, Institut Régional du Cancer Montpellier, ICM Val d'Aurelle
city: Nice
country: France
facility: Pôle de radiothérapie, Centre Antoine-Lacassagne
city: Paris
country: France
facility: Radiothérapie, CHU Pitié-Salpétrière
city: Paris
country: France
facility: Institut Curie, site Hôpital de Paris et site d'Orsay (Centre de protonthérapie)
city: Pessac
country: France
facility: Radiothérapie, Hôpital de Haut Lévêque, CHU Bordeaux
city: Reims
country: France
facility: Radiothérapie, CRLCC Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Saint-Herblain
country: France
facility: Radiothérapie, CRLCC René Gauducheau
city: St Priest en Jarez
country: France
facility: Radiothérapie, Institut de Cancérologie de la Loire Lucien Neuwirtz
city: Strasbourg
country: France
facility: Radiothérapie, CRLCC Paul Strauss
city: Toulouse
country: France
facility: Institut universitaire du cancer de Toulouse - Oncopole, Institut Claudius Regaud
city: Vandœuvre-lès-Nancy
country: France
facility: Radiothérapie, Institut de Cancérologie de Lorraine Alexis Vautrin
city: Villejuif
country: France
facility: Radiothérapie, Institut Gustave Roussy
Study officials:
affiliation: Centre Leon Berard
name: Pascal POMMIER, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Balosso J, Febvey-Combes O, Iung A, Lozano H, Alloh AS, Cornu C, Herve M, Akkal Z, Lievre M, Plattner V, Valvo F, Bono C, Fiore MR, Vitolo V, Vischioni B, Patin S, Allemand H, Gueyffier F, Margier J, Guerre P, Chabaud S, Orecchia R, Pommier P. A randomized controlled phase III study comparing hadrontherapy with carbon ions versus conventional radiotherapy - including photon and proton therapy - for the treatment of radioresistant tumors: the ETOILE trial. BMC Cancer. 2022 May 23;22(1):575. doi: 10.1186/s12885-022-09564-7.