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

Tracking Information

• First Submitted Date: July 18, 2016
• First Posted Date: July 20, 2016
• Last Update Posted Date: September 2, 2021
• Actual Study Start Date: December 23, 2017
• Estimated Primary Completion Date: December 23, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 18, 2016)

Progression free survival (PFS) [ Time Frame: up to 5 years or loss of follow-up ]

Starting point for PFS measurement is the randomization date

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 18, 2016)

• Grades of the CTCAE-V4.02 classification [ Time Frame: up to 5 years or loss of follow-up ]
  Tolerance
• EQ-5D questionnaire [ Time Frame: up to 5 years or loss of follow-up ]
  Quality of life
• 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)
• 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
• Overall survival [ Time Frame: up to 5 years or loss of follow-up ]
  delay of death of any cause accounted starting from randomization

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Malignant Tumors as Chordoma, Adenoid Cystic Carcinoma and Sarcoma

Intervention

• Radiation: Carbon ions therapy
  External radiotherapy by accelerated carbon nucleus in a specialized hadrontherapy center
• 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

Study Arms

• Experimental: Carbon ions therapy
  Radical and exclusive carbon ions radiotherapy
  Intervention: Radiation: Carbon ions therapy
• Active Comparator: Conventional radiotherapy
  Radical radiotherapy by Xrays and / or protons
  Intervention: Radiation: Advanced external radiotherapy by Xrays or protons

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 18, 2016): 250
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 23, 2026
• Estimated Primary Completion Date: December 23, 2026 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02838602
• Other Study ID Numbers: 2012-760
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hospices Civils de Lyon
• Original Responsible Party: Same as current
• Current Study Sponsor: Hospices Civils de Lyon
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Hospices Civils de Lyon
• Verification Date: September 2021