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

Study Overview
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Brief Summary
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Comparative study on surgery versus definitive radiation therapy in primary localized sacral chordoma

Detailed Description
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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

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

Conditions
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Chordoma

Intervention / Treatment
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* Other: Randomized Cohort
* Radiation: Prospective cohort


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Randomized Cohort<br>Participants who will decided to undergo to randomization, will receive surgical treatment or definitive radiotherapy according with randomization assignment | Other: Randomized Cohort<br>* 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<br>|
| Active Comparator: Prospective Cohort<br>Participants who will not decide to be randomized, will received the surgical or definite radiotherapy treatment according to their choice | Radiation: Prospective cohort<br>* Surgical treatment or definitive high dose radiotherapy will be selected by the patients and will be prospectively evaluated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse Free Survival (RFS) | The time from randomization or treatment start date to the date of local disease relapse, distant disease relapse, second primary malignancy or death from any cause, whichever occurred first. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | The time from randomization or treatment start date to the date of death from any cause | The patients will be followed in term of Overall Survival, for all the study period (expected average: 10 years) | 
| Survival Post Progression (SPP) | The time from local disease relapse, distant disease relapse or second primary malignancy, whichever occurred first, to the date of death from any cause | Expected average: 36 months | 
| Local Relapse Failure (LRF) | The time from randomization or treatment start date to the date of local disease relapse | Expected average: 60 months | 
| Distant Relapse Failure (DRF) | The time from randomization or treatment start date to the date of distant disease relapse | Expected average: 60 months | 
| Best Response rate to definitive radiotherapy | Best Response rate to definitive radiotherapy | At 12 months, 2 years and 5 years after radiotherapy | 
| Time to best response rate to definitive radiotherapy | Time to best response rate to definitive radiotherapy | At 12 months, 2 years and 5 years after radiotherapy | 
| Adverse Events Incidence | Adverse Events incidence | 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 | Evaluation of quality of life measured with Functional Assessment of Cancer Therapy General | every 6 months (expected average: 5 years) | 
| Evaluation of quality of life measured with Brief Inventory Pain questionnaires | Evaluation of quality of life measured with Brief Inventory Pain questionnaires | every 6 months (expected average: 5 years) |