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

Ependymoma Clinical Trial

— SBRT  

Official title:

Hypofractionated Stereotactic Radiation Treatments (SBRT) on Children, Teenagers and Young Adults Malignant Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02013297
• Other study ID #: SBRT
• Status: Completed
• Phase: N/A
• Start date: December 3, 2013
• Est. completion date: October 12, 2021

Study information

• Verified date: March 2022
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: October 12, 2021
• Est. primary completion date: April 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months to 20 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastasis
• Brain Neoplasms
• Ependymoma
• Lung Tumors
• Neoplasm Metastasis
• Neoplasms
• Spinal Cord Neoplasms
• Spinal Neoplasms
• Spinal Tumors

Intervention

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.

Locations

Country	Name	City	State
France	CHU Bordeaux - Hôpital Saint André	Bordeaux	Gironde
France	Centre François Baclesse	Caen	Calvados
France	Centre Oscar Lambret	Lille	Nord
France	Centre Léon Bérard	Lyon	Rhône
France	Hôpital La Timone	Marseille	Bouches Du Rhône
France	Institut de Cancérologie de Montpellier	Montpellier	Hérault
France	Centre Antoine Lacassagne	Nice	Alpes Maritimes
France	Institut Curie	Paris	Ile De France
France	Centre Eugène Marquis	Rennes	Ille Et Vilaine
France	Institut de Cancérologie de l'Ouest René Gauducheau	Saint Herblain	Loire Atlantique
France	Centre Paul Strauss	Strasbourg	Bas-Rhin
France	Centre Claudius Régaud	Toulouse	Haute Garonne
France	CHRU de Tours - Hôpital Bretonneau	Tours	Indre Et Loire
France	Institut de Cancérologie de Lorraine	Vandoeuvre-Lès-Nancy	Meurthe Et Moselle
France	Institut Gustave Roussy	Villejuif	Val De Marne

Sponsors (1)

Lead Sponsor	Collaborator
Centre Leon Berard

Country where clinical trial is conducted

France, 

References & Publications (22)

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. — View Citation

Combs SE, Behnisch W, Kulozik AE, Huber PE, Debus J, Schulz-Ertner D. Intensity Modulated Radiotherapy (IMRT) and Fractionated Stereotactic Radiotherapy (FSRT) for children with head-and-neck-rhabdomyosarcoma. BMC Cancer. 2007 Sep 13;7:177. — View Citation

Conter C, Carrie C, Bernier V, Geoffray A, Pagnier A, Gentet JC, Lellouch-Tubiana A, Chabaud S, Frappaz D. Intracranial ependymomas in children: society of pediatric oncology experience with postoperative hyperfractionated local radiotherapy. Int J Radiat Oncol Biol Phys. 2009 Aug 1;74(5):1536-42. doi: 10.1016/j.ijrobp.2008.09.051. Epub 2009 Apr 11. — View Citation

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. — View Citation

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. — View Citation

Giller CA, Berger BD, Pistenmaa DA, Sklar F, Weprin B, Shapiro K, Winick N, Mulne AF, Delp JL, Gilio JP, Gall KP, Dicke KA, Swift D, Sacco D, Harris-Henderson K, Bowers D. Robotically guided radiosurgery for children. Pediatr Blood Cancer. 2005 Sep;45(3):304-10. — View Citation

Grabb PA, Lunsford LD, Albright AL, Kondziolka D, Flickinger JC. Stereotactic radiosurgery for glial neoplasms of childhood. Neurosurgery. 1996 Apr;38(4):696-701; discussion 701-2. — View Citation

Hodgson DC, Goumnerova LC, Loeffler JS, Dutton S, Black PM, Alexander E 3rd, Xu R, Kooy H, Silver B, Tarbell NJ. Radiosurgery in the management of pediatric brain tumors. Int J Radiat Oncol Biol Phys. 2001 Jul 15;50(4):929-35. — View Citation

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. — View Citation

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. — View Citation

Lo SS, Sahgal A, Wang JZ, Mayr NA, Sloan A, Mendel E, Chang EL. Stereotactic body radiation therapy for spinal metastases. Discov Med. 2010 Apr;9(47):289-96. Review. — View Citation

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. — View Citation

Massimino M, Gandola L, Giangaspero F, Sandri A, Valagussa P, Perilongo G, Garrè ML, Ricardi U, Forni M, Genitori L, Scarzello G, Spreafico F, Barra S, Mascarin M, Pollo B, Gardiman M, Cama A, Navarria P, Brisigotti M, Collini P, Balter R, Fidani P, Stefanelli M, Burnelli R, Potepan P, Podda M, Sotti G, Madon E; AIEOP Pediatric Neuro-Oncology Group. Hyperfractionated radiotherapy and chemotherapy for childhood ependymoma: final results of the first prospective AIEOP (Associazione Italiana di Ematologia-Oncologia Pediatrica) study. Int J Radiat Oncol Biol Phys. 2004 Apr 1;58(5):1336-45. — View Citation

Merchant TE, Boop FA, Kun LE, Sanford RA. A retrospective study of surgery and reirradiation for recurrent ependymoma. Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):87-97. doi: 10.1016/j.ijrobp.2007.09.037. — View Citation

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. — View Citation

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.

Sharma MS, Kondziolka D, Khan A, Kano H, Niranjan A, Flickinger JC, Lunsford LD. Radiation tolerance limits of the brainstem. Neurosurgery. 2008 Oct;63(4):728-32; discussion 732-3. doi: 10.1227/01.NEU.0000325726.72815.22. — View Citation

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. — View Citation

Timmerman RD. An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol. 2008 Oct;18(4):215-22. doi: 10.1016/j.semradonc.2008.04.001. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SBRT treatment and toxicities related costs for 6 months after SBRT	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.	6 months after inclusion
Other	Cost/Efficacy ratio between 2 modalities of SBRT treatment of ependymoma at 6 months after treatment	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	6 months after inclusion
Other	Cost/Efficacy ratio between 2 modalities of SBRT treatment of ependymoma at 12 months after treatment	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	12 months after inclusion
Other	Cost/Efficacy ratio between 2 modalities of SBRT treatment of ependymoma at 24 months after treatment	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	24 months after inclusion
Primary	Efficacy of SBRT assessed 6 months after treatment	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)	6 months after inclusion
Secondary	Efficacy of SBRT assessed between 1,5 and 3 months after treatment	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	Between 1,5 and 3 months after inclusion
Secondary	Progressive Free Survival	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)	From the date of inclusion to the date of progression
Secondary	Overall Survival	Calculated from the date of inclusion to the date of death from any cause (Up to 5 years since the first inclusion)	From the date of inclusion to the date of death (Up to 5 years since the first inclusion)
Secondary	Short time Safety profile of SBRT	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	From inclusion to 3 months after inclusion
Secondary	Long term Safety profile of SBRT	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	after 24 months after inclusion
Secondary	Efficacy of SBRT assessed 12 months after treatment	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	12 months after inclusion
Secondary	Efficacy of SBRT assessed 24 months after treatment	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	24 months after inclusion
Secondary	Medium time Safety profile of SBRT	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	Between 3 months and 24 months after inclusion