Sacral Chordoma: Surgery Versus Definitive Radiation Therapy in Primary Localized Disease

Официальное название

Title of Study: SAcral Chordoma: a Randomized & Observational Study on Surgery Versus Definitive Radiation Therapy in Primary Localized Disease (SACRO)

Обзор

Comparative study on surgery versus definitive radiation therapy in primary localized sacral chordoma

Подробное описание

International, multicenter, comparative, open-label, parallel-group, mixed Observational-Randomized Controlled Trial.

All the patients, who are candidate for the study will receive full information on the characteristics, potential effectiveness and side effects of the two alternatives treatments: radiotherapy (RT) and surgical treatment Eligible patients will be asked to be randomized in order to receive treatment A (surgery, with or without RT) or treatment B (definitive RT) Who will refuse randomization will be included in the Prospective Cohort Study (PCS) and will be treated accordingly to their choice (treatment option A or treatment option B).

The same radiotherapy and surgical regimen will be administered in the PCS and in the Randomized Clinical Trial (RCT) cohort

Вмешательства

• Другое Randomized Cohort
  Surgical treatment with different approach, based on the characteristics of the tumor or definitive high dose radiotherapy (carbon ion radiotherapy, proton-therapy, mixed photons-proton therapy) will be assigned by randomization
• Лучевая терапия Prospective cohort
  Surgical treatment or definitive high dose radiotherapy will be selected by the patients and will be prospectively evaluated

Первичные конечные точки

• Relapse Free Survival (RFS) [Срок оценки: 5 years]

Вторичные конечные точки (9)

• Overall Survival (OS) [Срок оценки: The patients will be followed in term of Overall Survival, for all the study period (expected average: 10 years)]
• Survival Post Progression (SPP) [Срок оценки: Expected average: 36 months]
• Local Relapse Failure (LRF) [Срок оценки: Expected average: 60 months]
• Distant Relapse Failure (DRF) [Срок оценки: Expected average: 60 months]
• Best Response rate to definitive radiotherapy [Срок оценки: At 12 months, 2 years and 5 years after radiotherapy]
• Time to best response rate to definitive radiotherapy [Срок оценки: At 12 months, 2 years and 5 years after radiotherapy]
• Adverse Events Incidence [Срок оценки: At end of treatment , 6 months , 12 months 2 years and 5 years after surgery or radiotherapy]
• Evaluation of quality of life measured with Functional Assessment of Cancer Therapy General [Срок оценки: every 6 months (expected average: 5 years)]
• Evaluation of quality of life measured with Brief Inventory Pain questionnaires [Срок оценки: every 6 months (expected average: 5 years)]

Критерии участия

Критерии включения

• Histologically confirmed diagnosis (brachyury expression) of primary sacral chordoma,of any diameter and arising at any site from S1 to coccyx.
• Age≥18years
• ECOG-performance status (PS) 0-2
• No previous antineoplastic therapy
• Macroscopic tumor detectable at MRI/CT scan
• Patient amenable for surgery
• Patient amenable for RT
• Written informed consent given before the enrolment, according to International Conference on Harmonisation/good clinical practice (ICH/GCP).

Критерии исключения

• Distant metastasis
• Inability to maintain treatment position
• Prior radiotherapy to the pelvic region
• Prior therapy for sacral chordoma (including surgery, cryoablation, hyperthermia, etc)
• Local conditions that increase the risk of RT toxicity (tumor ulcerated skin infiltration, non-healing soft tissue infection, fistula in treatment field)
• Rectal wall infiltration
• General conditions that increase the risk of RT toxicity (active sclerodermia, xeroderma pigmentosum, cutaneous porphyria)
• Presence of a second active cancer (with the exception of non-melanoma skin cancer in-situ cervix neoplasia and other in-situ neoplasia)
• Severe comorbidities resulting in a prognosis of less than 6 months
• Inability to give informed consent
• Other malignancy within the last 5 years
• Performance status ≥ 2 (ECOG).
• Significant cardiovascular disease (for example, dyspnea > 2 NYHA)
• Significant systemic diseases grade >3 on the NCI-CTCAE v4.03 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity
• Women who are pregnant or breast-feeding
• Psychological, familial, social or geographic circumstances that limit the patient's ability to comply with the protocol or informed consent

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Италия · 9 центров

• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan
• Istituto Ortopedico Rizzoli — Bologna
• Azienda Ospedaliero-Universitaria Careggi — Florence
• Istituto Clinico Humanitas — Milan
• I.R.C.C.S. Istituto Ortopedico Galeazzi — Milan
• Centro Nazionale di Adroterapia Oncologica - CNAO — Pavia
• II Clinica Universitaria Ortopedia e Traumatologia AO Pisa — Pisa
• Istituto Regina Elena - IFO — Rome
• … и ещё 1 центр

Испания · 5 центров

• H. Val D'Hebron — Barcelona
• Hosptial San Pau — Barcelona
• H. San Carlos — Madrid
• Hospital Universitario Virgen del Rocío — Seville
• Hospital Universitario Doctor Peset — Valencia

Германия · 4 центра

• Medical Faculty Carl Gustav Carus Faculty of Medicine, Department of Radiation Oncology, — Dresden
• University Hospital Carl Gustav Carus Dresden — Dresden
• University Hospital Essen. West German Proton Therapy Center Essen — Essen
• Heidelberg Ion-Beam Therapy Center - HIT — Heidelberg

Австрия · 2 центра

• Medical University of Graz — Graz
• EBG GmbH MedAustron — Wiener Neustadt

Нидерланды · 2 центра

• Netherlands Cancer Institute — Amsterdam
• Leiden University Medical Center — Leiden

Великобритания · 2 центра

• The Royal Orthopaedic Hospital — Birmingham
• Royal National Orthopaedic Hospital — London

Венгрия · 1 центр

• National Center for Spinal Disorders — Budapest

Япония · 1 центр

• Saitama Medical Center — Saitama

Норвегия · 1 центр

• Norwegian Radium Hospital/Oslo Univeristi Hospital — Oslo

Польша · 1 центр

• Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie — Warsaw

Публикации

• Stiller CA, Trama A, Brewster DH, Verne J, Bouchardy C, Navarro C, Chirlaque MD, Marcos-Gragera R, Visser O, Serraino D, Weiderpass E, Dei Tos AP, Ascoli V; RARECARE Working Group. Descriptive epidemiology of Kaposi sarcoma in Europe. Report from the RARECARE project. Cancer Epidemiol. 2014 Dec;38(6):670-8. doi: 10.1016/j.canep.2014.09.009. Epub 2014 Oct 22. PMID 25454979
• Tirabosco R, Mangham DC, Rosenberg AE, Vujovic S, Bousdras K, Pizzolitto S, De Maglio G, den Bakker MA, Di Francesco L, Kalil RK, Athanasou NA, O'Donnell P, McCarthy EF, Flanagan AM. Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. Am J Surg Pathol. 2008 Apr;32(4):572-80. doi: 1 PMID 18301055
• Brien EW, Mirra JM, Ippolito V. Chondroblastoma arising from a nonepiphyseal site. Skeletal Radiol. 1995 Apr;24(3):220-2. doi: 10.1007/BF00228930. PMID 7610417
• Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C, Flanagan AM. Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol. 2006 Jun;209(2):157-65. doi: 10.1002/path.1969. PMID 16538613
• Miozzo M, Dalpra L, Riva P, Volonta M, Macciardi F, Pericotti S, Tibiletti MG, Cerati M, Rohde K, Larizza L, Fuhrman Conti AM. A tumor suppressor locus in familial and sporadic chordoma maps to 1p36. Int J Cancer. 2000 Jul 1;87(1):68-72. PMID 10861454
• Kelley MJ, Korczak JF, Sheridan E, Yang X, Goldstein AM, Parry DM. Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33. Am J Hum Genet. 2001 Aug;69(2):454-60. doi: 10.1086/321982. Epub 2001 Jul 10. PMID 11452362
• Lee-Jones L, Aligianis I, Davies PA, Puga A, Farndon PA, Stemmer-Rachamimov A, Ramesh V, Sampson JR. Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2. Genes Chromosomes Cancer. 2004 Sep;41(1):80-5. doi: 10.1002/gcc.20052. PMID 15236319
• Dutton RV, Singleton EB. Tuberous sclerosis: a case report with aortic aneurysm and unusual rib changes. Pediatr Radiol. 1975 Jun 13;3(3):184-6. doi: 10.1007/BF01006909. PMID 1233436

Идентификаторы

NCT: NCT02986516 · ISG SACRO

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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