Study of SBRT Efficacy on Intra and Extra -Cranial Tumors or Metastasis in Pediatrics Population (SBRT Pediatrics) (SBRT)

• ClinicalTrials.gov Identifier: NCT02013297
• Recruitment Status: Completed
• First Posted: December 17, 2013
• Last Update Posted: March 8, 2022
• Sponsor: Centre Leon Berard
• Information provided by (Responsible Party): Centre Leon Berard

Study Description

Brief Summary:

The purpose of this study is to evaluate the efficacy of hypofractionated stereotactic radiation treatments (SBRT) on children, teenagers and young adults malignant tumors.

Condition or disease	Intervention/treatment	Phase
Brain Metastasis; Spinal Tumors; Lung Tumors; Ependymoma	Radiation: SBRT treatment	Not Applicable

Detailed Description:

SBRT (Stereotactic Body Radiation Therapy) is a radiotherapy treatment which involves the delivery of a single high dose radiation treatment or a few fractionated radiation treatments (usually up to 5). A high potent biological dose of radiation is delivered to the tumor improving the cure rates for the tumor, in a manner previously not achievable by standard conventional radiation therapy.

For adult patients, the "Haute Authorité de Santé" (HAS) validates some indications for this treatment which are the followings :

• Few primary or secondary brain tumors, which cannot be surgically removed
• Spinal tumors
• Primary bronchopulmonary tumors T1 T2 N0 M0 and pulmonary metastasis with slow growth and controled primary tumor.

For pediatrics patients, no indication is now validated by HAS. Indications validated for adults are rare in pediatrics but not exceptional, and in such cases efficient alternative treatments does not exist.

In consequence, and regarding the good results obtained in adult patients, it seems very important to validate the efficacy of this treatment on pediatrics population

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hypofractionated Stereotactic Radiation Treatments (SBRT) on Children, Teenagers and Young Adults Malignant Tumors
• Actual Study Start Date: December 3, 2013
• Actual Primary Completion Date: April 3, 2020
• Actual Study Completion Date: October 12, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: SBRT treatment; According to the site to irradiate and to local constraints, SBRT consist in 1 to 8 fractions of 5 to 18 Gy

Radiation: SBRT treatment; For Brain metastasis the SBRT treatment consists on 3 fractions of 8 Gy or 5 fractions of 7 Gy or 1 fraction of 18 Gy for a single metastasis which is less than 20 mm. For primary or secondary pulmonary tumors the SBRT treatment consists on 3 fractions of 15 Gy or 5 fractions of 10 Gy for peripheral lesions and on 5 fractions of 8 Gy for proximal lesions. For primary or secondary spinal or para-spinal tumors the SBRT treatment consists on 3 fractions of 9 Gy or 5 fractions of 7 Gy. For previously irradiated tumors (same locations) the SBRT treatment consists on 5 to 8 fractions of 5 Gy. For relapsed Ependymoma previously irradiated the SBRT treatment will be allocated by surgical stratified randomization and consists on either 3 fractions of 8 Gy or 5 fractions of 5 Gy.

Outcome Measures

Primary Outcome Measures :

1. Efficacy of SBRT assessed 6 months after treatment [ Time Frame: 6 months after inclusion ]
   The treatment efficacy is assessed by calculation of local control rate of irradiated locations according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (complete response + partial response + stable disease)

Secondary Outcome Measures :

1. Efficacy of SBRT assessed between 1,5 and 3 months after treatment [ Time Frame: Between 1,5 and 3 months after inclusion ]
   The treatment efficacy is assessed by calculation of local control rate of irradiated locations according to RECIST version 1.1 criteria (complete response + partial response + stable disease) between 1,5 and 3 months after treatment
2. Progressive Free Survival [ Time Frame: From the date of inclusion to the date of progression ]
   Calculated from the date of inclusion to the date defined as the first documented disease progression, or second cancer appearance, or death from any cause (Up to 5 years since the first inclusion)
3. Overall Survival [ Time Frame: From the date of inclusion to the date of death (Up to 5 years since the first inclusion) ]
   Calculated from the date of inclusion to the date of death from any cause (Up to 5 years since the first inclusion)
4. Short time Safety profile of SBRT [ Time Frame: From inclusion to 3 months after inclusion ]
   Toxicities appeared during SBRT treatment and up to 3 months after SBRT. Toxicities will be assessed by the evaluation of intensity and incidence of the Adverse Events (AE) displayed by patients. The intensity of each AE will be classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
5. Long term Safety profile of SBRT [ Time Frame: after 24 months after inclusion ]
   Toxicities appeared after 24 months after inclusion. The outcome measure concerns toxicities appeared after the study following period. Toxicities will be assessed by the evaluation of intensity and incidence of the Adverse Events (AE) displayed by patients. The intensity of each AE will be classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
6. Efficacy of SBRT assessed 12 months after treatment [ Time Frame: 12 months after inclusion ]
   The treatment efficacy is assessed by calculation of local control rate of irradiated locations according to RECIST version 1.1 criteria (complete response + partial response + stable disease) at 12 months after treatment
7. Efficacy of SBRT assessed 24 months after treatment [ Time Frame: 24 months after inclusion ]
   The treatment efficacy is assessed by calculation of local control rate of irradiated locations according to RECIST version 1.1 criteria (complete response + partial response + stable disease) at 24 months after treatment
8. Medium time Safety profile of SBRT [ Time Frame: Between 3 months and 24 months after inclusion ]
   Toxicities appeared between 3 months and 24 months after treatment. Toxicities will be assessed by the evaluation of intensity and incidence of the Adverse Events (AE) displayed by patients. The intensity of each AE will be classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Other Outcome Measures:

1. SBRT treatment and toxicities related costs for 6 months after SBRT [ Time Frame: 6 months after inclusion ]
   The SBRT treatment related costs will be evaluated by a "microcosting" method which take into account, in particular, the irradiation duration seance, the time for the mobilized staff, the kind of equipment required, the duration of related AE hospitalizations.
2. Cost/Efficacy ratio between 2 modalities of SBRT treatment of ependymoma at 6 months after treatment [ Time Frame: 6 months after inclusion ]

   2 modalities of SBRT are compared in patients with an ependymoma (3 fractions of 8 Gy versus 5 fractions of 5 Gy). It will be calculated the cost/efficacity ratio for the avoided toxicity 6 months after SBRT.

   The costs will be evaluated by the data from french social security system, from homogeneous group of patients and from general classification of professional acts

3. Cost/Efficacy ratio between 2 modalities of SBRT treatment of ependymoma at 12 months after treatment [ Time Frame: 12 months after inclusion ]

   2 modalities of SBRT are compared in patients with an ependymoma (3 fractions of 8 Gy versus 5 fractions of 5 Gy). It will be calculated :

   • the cost/efficacity per gained year of life without relapse after 12 months after SBRT
   • the cost/efficacity per gained year of life without disease after 12 months after SBRT.

   The costs will be evaluated by the data from french social security system, from homogeneous group of patients and from general classification of professional acts

4. Cost/Efficacy ratio between 2 modalities of SBRT treatment of ependymoma at 24 months after treatment [ Time Frame: 24 months after inclusion ]

   2 modalities of SBRT are compared in patients with an ependymoma (3 fractions of 8 Gy versus 5 fractions of 5 Gy). It will be calculated :

   • the cost/efficacity per gained year of life without relapse after 24 months after SBRT
   • the cost/efficacity per gained year of life without disease after 24 months after SBRT.

   The costs will be evaluated by the data from french social security system, from homogeneous group of patients and from general classification of professional acts

Eligibility Criteria

• Ages Eligible for Study: 18 Months to 20 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

INCLUSION CRITERIA:

• 18 months ≤ age ≤ 20 years
• Malignant primary tumor, histologically or cytologically proven
• Systemic disease under control or with slow evolution
• Written indication of SBRT according to local pediatrics meeting and national Radiotherapy (RT) web conference
• Performance Status ≤ 2 according to Eastern Cooperative Oncology Group (ECOG)

• Sites

  • Brain metastasis (≤ 3 on MRI) not suitable for surgery, without hemorrhage, less than 3 cm each, not in the brain stem
  • Primary or secondary spinal/para spinal metastasis (≤ 3), not suitable for surgery or with a non operable macroscopic residue, less than 5 cm
  • Lung metastasis (≤ 3), less than 5 cm, not eligible for surgery, or macroscopic residue not suitable for surgery
  • Previously irradiated relapsing isolated primitive/secondary tumor (intra cranial or extra cranial), with no possible surgery, or macroscopic residue.
• Affiliation to a social security scheme
• Signed Informed consent by patient or parents and patient

IN ADDITION FOR RELAPSING EPENDYMOMA:

• Histologically proven local ependymoma at diagnosis
• Previously irradiated ependymoma
• Exclusive local relapse in previously irradiated site
• Review of operability at time of relapse by a multidisciplinary staff
• Relapse must be confirmed by a neuro-oncology multidisciplinary staff, on MRI evolutivity characteristics
• Time to relapse after previous irradiation ≥ 1 year

NON-INCLUSION CRITERIA :

• Concomitant chemotherapy
• No evaluable target (except for completely resected ependymomas)
• Pregnancy
• Follow-up impossible

IN ADDITION FOR RELAPSING EPENDYMOMAS:

• Metastatic patient at diagnosis and/or at relapse
• Complete remission never obtained

NON-RANDOMIZATION DOSIMETRIC CRITERIA (ONLY FOR EPENDYMOMA)

• Cumulative doses to brain stem ≥ 115 Gy
• Tumor volume at relapse ≥ 30 cm3
• Primary RT dose + Re-irradiation dose more than 112 Gy
• Cumulative dose to the chiasma > 54 Gy
• Cumulative dose to any point of the brain > 115 Gy

Contacts and Locations

Locations

France

Centre Antoine Lacassagne

Nice, Alpes Maritimes, France, 06050

Centre Paul Strauss

Strasbourg, Bas-Rhin, France, 67805

Hôpital La Timone

Marseille, Bouches Du Rhône, France, 13500

Centre François Baclesse

Caen, Calvados, France, 14000

CHU Bordeaux - Hôpital Saint André

Bordeaux, Gironde, France, 33000

Centre Claudius Régaud

Toulouse, Haute Garonne, France, 31052

Institut de Cancérologie de Montpellier

Montpellier, Hérault, France, 34298

Institut Curie

Paris, Ile De France, France, 75231

Centre Eugène Marquis

Rennes, Ille Et Vilaine, France, 35062

CHRU de Tours - Hôpital Bretonneau

Tours, Indre Et Loire, France, 37044

Institut de Cancérologie de l'Ouest René Gauducheau

Saint Herblain, Loire Atlantique, France, 44805

Institut de Cancérologie de Lorraine

Vandoeuvre-Lès-Nancy, Meurthe Et Moselle, France, 54511

Centre Oscar Lambret

Lille, Nord, France, 59020

Centre Léon Bérard

Lyon, Rhône, France, 69373

Institut Gustave Roussy

Villejuif, Val De Marne, France, 94805

Sponsors and Collaborators

Centre Leon Berard

Investigators

• Principal Investigator: Line CLAUDE, Doctor; Centre Leon Berard

More Information

Publications:

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Rapport ANAES : Evaluation clinique et économique de la radiochirurgie intra cranienne en conditions stéréotaxique - Rapport ANAES/Service évaluation des technologies-évaluation économique: 2000.

Rapport HAS : Radiothérapie extra crânienne en conditions stéréotaxiques - Décembre 2006: 2006.

Maranzano E, Anselmo P, Casale M, Trippa F, Carletti S, Principi M, Loreti F, Italiani M, Caserta C, Giorgi C. Treatment of recurrent glioblastoma with stereotactic radiotherapy: long-term results of a mono-institutional trial. Tumori. 2011 Jan-Feb;97(1):56-61.

Minniti G, Armosini V, Salvati M, Lanzetta G, Caporello P, Mei M, Osti MF, Maurizi RE. Fractionated stereotactic reirradiation and concurrent temozolomide in patients with recurrent glioblastoma. J Neurooncol. 2011 Jul;103(3):683-91. doi: 10.1007/s11060-010-0446-8. Epub 2010 Nov 5.

Torok JA, Wegner RE, Mintz AH, Heron DE, Burton SA. Re-irradiation with radiosurgery for recurrent glioblastoma multiforme. Technol Cancer Res Treat. 2011 Jun;10(3):253-8.

Zacharoulis S, Ashley S, Moreno L, Gentet JC, Massimino M, Frappaz D. Treatment and outcome of children with relapsed ependymoma: a multi-institutional retrospective analysis. Childs Nerv Syst. 2010 Jul;26(7):905-11. doi: 10.1007/s00381-009-1067-4. Epub 2009 Dec 29.

Kano H, Yang HC, Kondziolka D, Niranjan A, Arai Y, Flickinger JC, Lunsford LD. Stereotactic radiosurgery for pediatric recurrent intracranial ependymomas. J Neurosurg Pediatr. 2010 Nov;6(5):417-23. doi: 10.3171/2010.8.PEDS10252.

Liu AK, Foreman NK, Gaspar LE, Trinidad E, Handler MH. Maximally safe resection followed by hypofractionated re-irradiation for locally recurrent ependymoma in children. Pediatr Blood Cancer. 2009 Jul;52(7):804-7. doi: 10.1002/pbc.21982.

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Chawla S, Schell MC, Milano MT. Stereotactic body radiation for the spine: a review. Am J Clin Oncol. 2013 Dec;36(6):630-6. doi: 10.1097/COC.0b013e31822dfd71. Review.

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Siva S, MacManus M, Ball D. Stereotactic radiotherapy for pulmonary oligometastases: a systematic review. J Thorac Oncol. 2010 Jul;5(7):1091-9. doi: 10.1097/JTO.0b013e3181de7143. Review.

Fogh SE, Andrews DW, Glass J, Curran W, Glass C, Champ C, Evans JJ, Hyslop T, Pequignot E, Downes B, Comber E, Maltenfort M, Dicker AP, Werner-Wasik M. Hypofractionated stereotactic radiation therapy: an effective therapy for recurrent high-grade gliomas. J Clin Oncol. 2010 Jun 20;28(18):3048-53. doi: 10.1200/JCO.2009.25.6941. Epub 2010 May 17. Erratum in: J Clin Oncol. 2010 Sep 20;28(27):4280.

Flannery T, Kano H, Martin JJ, Niranjan A, Flickinger JC, Lunsford LD, Kondziolka D. Boost radiosurgery as a strategy after failure of initial management of pediatric primitive neuroectodermal tumors. J Neurosurg Pediatr. 2009 Mar;3(3):205-10. doi: 10.3171/2008.11.PEDS08268.

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• Responsible Party: Centre Leon Berard
• ClinicalTrials.gov Identifier: NCT02013297
• Other Study ID Numbers: SBRT
• First Posted: December 17, 2013
• Last Update Posted: March 8, 2022
• Last Verified: March 2022

Keywords provided by Centre Leon Berard:

Pediatrics; SBRT; Brain metastasis; Pulmonary metastasis; Spinal metastasis; Pulmonary primary tumor; Spinal primary tumor; Relapsed ependymoma; Relapsed irradiated tumors; Local control rate; Safety; Overall survival; Progression Free Survival

Additional relevant MeSH terms:

Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Ependymoma; Spinal Cord Neoplasms; Spinal Neoplasms; Neoplastic Processes; Pathologic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Spinal Cord Diseases; Bone Neoplasms; Bone Diseases; Musculoskeletal Diseases; Spinal Diseases