Randomized Carbon Ions vs Standard Radiotherapy for Radioresistant Tumors (ETOILE)

• ClinicalTrials.gov Identifier: NCT02838602
• Recruitment Status: Recruiting
• First Posted: July 20, 2016
• Last Update Posted: September 2, 2021
• Sponsor: Hospices Civils de Lyon
• Information provided by (Responsible Party): Hospices Civils de Lyon

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Malignant Tumors as Chordoma, Adenoid Cystic Carcinoma and Sarcoma	Radiation: Carbon ions therapy; Radiation: Advanced external radiotherapy by Xrays or protons	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Transnational Randomized Study Comparing Carbon Ions Therapy Versus Conventional Radiotherapy - Including Protontherapy - for the Treatment of Radioresistant Tumors
• Actual Study Start Date: December 23, 2017
• Estimated Primary Completion Date: December 23, 2026
• Estimated Study Completion Date: December 23, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Carbon ions therapy; Radical and exclusive carbon ions radiotherapy	Radiation: Carbon ions therapy; External radiotherapy by accelerated carbon nucleus in a specialized hadrontherapy center
Active Comparator: Conventional radiotherapy; Radical radiotherapy by Xrays and / or protons	Radiation: Advanced external radiotherapy by Xrays or protons; 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

Outcome Measures

Primary Outcome Measures :

1. Progression free survival (PFS) [ Time Frame: up to 5 years or loss of follow-up ]
   Starting point for PFS measurement is the randomization date

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Pascal POMMIER, MD; (0)4 78 78 51 66 ext +33; pascal.pommier@lyon.unicancer.fr

Locations

France

CHU Amiens - Hôpital Sud; Recruiting

Amiens, France, 80054

Contact: Claude KRZISCH, MD

Principal Investigator: Claude KRZISCH, MD

Radiothérapie, CLCC François Baclesse; Recruiting

Caen, France, 14076

Contact: Juliette THARIAT, MD

Principal Investigator: Juliette THARIAT, MD

Sub-Investigator: Dinu STEFAN, MD

Sub-Investigator: Delphine LEROUGE, MD

Sub-Investigator: Bernard GERY, MD

Sub-Investigator: Laura MOISE, MD

Sub-Investigator: Sabine NOAL, MD

Sub-Investigator: Jacques BALOSSO, MD

Radiothérapie, CRLCC Jean Perrin; Not yet recruiting

Clermont-Ferrand, France, 63011

Contact: Fanny MARTIN

Principal Investigator: Fanny MARTIN, MD

Sub-Investigator: Michel LAPEYRE, MD

Sub-Investigator: Jessica MIROIR, MD

Radiothérapie, CRLCC GF Leclerc; Recruiting

Dijon, France, 21034

Contact: Gilles TRUC, MD 03.80.73.75.18

Principal Investigator: Gilles TRUC, MD

Sub-Investigator: Noémie VULQUIN, MD

Sub-Investigator: David THIBOUW, MD

Sub-Investigator: Caroline AMOYAL, MD

Radiothérapie, Hôpital A. Michallon, CHU de Grenoble; Recruiting

Grenoble, France, 38043

Contact: Camille, Olivier VERRY, MD 04.76.76.54.35

Principal Investigator: Camille, Olivier VERRY, MD

Sub-Investigator: Julie VILLA, MD

Sub-Investigator: Jacques BALOSSO, MD

Sub-Investigator: Carole IRIART, MD

Sub-Investigator: Violaine BRUN-BARONNAT, MD

Radiothérapie, CRLCC Oscar Lambret; Recruiting

Lille, France, 59020

Contact: Xavier MIRABEL, MD 03.20.29.55.98

Principal Investigator: Xavier MIRABEL, MD

Sub-Investigator: Raphaëlle MOUTTET-AUDOUARD, MD

Sub-Investigator: Abel CORDOBA, MD

Sub-Investigator: Xavier LIEM, MD

Sub-Investigator: David PASQUIER, MD

Radiothérapie, CRLCC Léon Bérard; Recruiting

Lyon, France, 69373

Contact: Pascal POMMIER, MD (0)4 78 78 51 66 ext +33 pascal.pommier@lyon.unicancer.fr

Principal Investigator: Pascal POMMIER, MD

Sub-Investigator: Marie-Pierre SUNYACH, MD

Sub-Investigator: Vincent GREGOIRE, MD

Radiothérapie, CRLCC Institut Paoli Calmettes; Not yet recruiting

Marseille, France, 13009

Contact: Laurence MOUREAU-ZABOTTO, MD 04.91.22.36.37

Principal Investigator: Laurence MOUREAU-ZABOTTO, MD

Radiothérapie, Institut Régional du Cancer Montpellier, ICM Val d'Aurelle; Recruiting

Montpellier, France, 34298

Contact: Pierre BOISSELIER, MD

Principal Investigator: Pierre BOISSELIER, MD

Pôle de radiothérapie, Centre Antoine-Lacassagne; Recruiting

Nice, France, 06189

Contact: Alexander FALK, MD

Principal Investigator: Alexander FALK, MD

Sub-Investigator: Jérôme DOYEN, MD

Sub-Investigator: Pierre-Yves BONDIAU, MD

Sub-Investigator: Karen BENEZERY, MD

Radiothérapie, CHU Pitié-Salpétrière; Not yet recruiting

Paris, France, 75013

Contact: Loïc FEUVRET 01.42.17.81.71

Principal Investigator: Loïc FEUVRET, MD

Institut Curie, site Hôpital de Paris et site d'Orsay (Centre de protonthérapie); Not yet recruiting

Paris, France, 75231

Contact: Rémi DENDALE, MD

Principal Investigator: Rémi DENDALE, MD

Sub-Investigator: Claire ALAPETITE, MD

Radiothérapie, Hôpital de Haut Lévêque, CHU Bordeaux; Not yet recruiting

Pessac, France, 33604

Contact: Charles DUPIN, MD

Principal Investigator: Charles DUPIN, MD

Sub-Investigator: Huchet AYMERI, MD

Radiothérapie, CRLCC Institut Jean Godinot; Recruiting

Reims, France, 51726

Contact: Stéphanie SERVAGI-VERNAT, MD

Principal Investigator: Stéphanie SERVAGI-VERNAT, MD

Centre Eugene Marquis; Not yet recruiting

Rennes, France, 35000

Contact: Joël CASTELLI, MD

Principal Investigator: Joël CASTELLI, MD

Radiothérapie, CRLCC René Gauducheau; Not yet recruiting

Saint-Herblain, France, 44805

Contact: Augustin MERVOYER, MD 02.40.67.99.30

Principal Investigator: Augustin MERVOYER, MD

Sub-Investigator: Nadia WIAZZANE, MD

Radiothérapie, Institut de Cancérologie de la Loire Lucien Neuwirtz; Recruiting

St Priest en Jarez, France, 42270

Contact: Nicolas MAGNE, MD

Principal Investigator: Nicolas MAGNE, MD

Sub-Investigator: Amel REHAILIA-BLANCHARD, MD

Sub-Investigator: Grégoire PIGNE, MD

Radiothérapie, CRLCC Paul Strauss; Recruiting

Strasbourg, France, 67065

Contact: Georges NOEL, MD 03.88.25.24.71

Principal Investigator: Georges NOEL, MD

Institut universitaire du cancer de Toulouse - Oncopole, Institut Claudius Regaud; Recruiting

Toulouse, France, 31059

Contact: Anne DUCASSOU, MD

Principal Investigator: Anne DUCASSOU, MD

Principal Investigator: Anne LAPRIE, MD

Sub-Investigator: Martine DELANNES, MD

Radiothérapie, Institut de Cancérologie de Lorraine Alexis Vautrin; Recruiting

Vandœuvre-lès-Nancy, France, 54500

Contact: Guillaume VOGIN, MD 03.83.59.84.27

Principal Investigator: Guillaume VOGIN, MD

Sub-Investigator: Sophie RENARD, MD

Radiothérapie, Institut Gustave Roussy; Not yet recruiting

Villejuif, France, 94805

Contact: Cécile LE PECHOUX, MD 01.42.11.42.11

Principal Investigator: Cécile LE PECHOUX, MD

Sub-Investigator: Stéphanie BOLLE, MD

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators

• Principal Investigator: Pascal POMMIER, MD; Centre Leon Berard

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Hospices Civils de Lyon
• ClinicalTrials.gov Identifier: NCT02838602
• Other Study ID Numbers: 2012-760
• First Posted: July 20, 2016
• Last Update Posted: September 2, 2021
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hospices Civils de Lyon:

carbon ions therapy; radiotherapy; radioresistant tumors; cancer; randomized trial

Additional relevant MeSH terms:

Carcinoma, Adenoid Cystic; Chordoma; Neoplasms; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Germ Cell and Embryonal