Reduction of Pain Symptoms With Stereotactic Radiotherapy on Bone Metastases

NCT ID: NCT03597984

Last Updated: 2019-07-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 330 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-01
• Study Completion Date: 2020-12-28

Brief Summary

Interventional study without medicinal, randomized 1: 1 open-label, multicenter, phase 3 to evaluate the response in terms of reduction of pain symptomatology from bone metastases, comparing the conformational radiotherapy (3D-CRT) administered in conventional fractionation vs. extracranial stereotactic radiotherapy (SBRT) administered with concomitant integrated simultaneous boost (Simultaneous Integrated Boost-SIB)

Detailed Description

Palliative antalgic oncological treatments, e.g. For patients in the chronic-evolutionary phase of the disease with need for pain control, are a serious problem from the point of view: management, clinical and scientific research. However, they are affecting an ever-increasing volume of patients due to the increased incidence of cancer in all its phases and the potential chronicity of illness linked to new therapies.

The use of palliative anti-radiation radiotherapy treatments potentially involves up to 40% of patients in a Radiotherapy Center. Radiotherapy is commonly used in palliative treatment of symptomatic bone metastases (Furfari A, 2017) being an effective treatment to improve symptoms and consequently improve the quality of life (QoL) of these patients. Due to the peculiar characteristics of the patients who need these treatments, scientific research aimed at optimizing these therapies is a need for assistance and even ethics.

Ideally, this treatment should be as short as possible to re-direct them to systemic therapies or to home care or long-term care systems (e.g.: Hospice). In order to deliver a clinically effective dose in a short period of time, hypofractionated regimens must be used. Stereotactic radiotherapy is a type of radiotherapy that allows to deliver a high equivalent biological dose in a highly conformed manner, with a favorable toxicity profile (Correa RJ, 2016), and generally in a few fractions. The possibility of using special techniques such as stereotactic radiotherapy has been investigated in several phase 2 studies, in terms of symptom response with good results at 3 months (van der Velden JM, 2016) (Murai T1, 2014) (Braam P , 2016) (Deodato F, 2014) (Ryu S, 2014). Further studies have suggested, in order to better manage the toxicity profile linked to the hypofractioned regimen, the possibility of using a hypofractionated regimen over the entire bone compartment and going to over-dose with a stereotaxic regimen only the macroscopically visible disease to the instrumental examinations. In particular, in patients with favorable prognostic scores, this regimen would improve the possible onset of acute and late complications. Although there are indications in the literature (generated by the Consensus Conference) about the radiation treatment schedules to be preferred, there is no globally coded and clinically applied therapeutic prescription standard (Chow E1 & Party, 2012). The most commonly applied conventional radiation treatment schedules include: i) 8 Gy in 1 therapy session; ii) 20 Gy in 5 therapy sessions; iii) 30 Gy in 10 therapy sessions.

With the same pain control, multiple fractionation boards report, according to some authors, better symptom control over time and are therefore very often preferred for patients with a prognosis> 6 months. Routine use of prognostic scores to characterize life expectancy and define the most appropriate treatment regimen is very rarely used in everyday clinical practice.

Modern oncology radiotherapy can take advantage of advanced technologies and exploit the personalization of treatments. To date, some randomized trials are underway investigating the role of stereotactic radiotherapy for these patients compared to conventional approaches, but not all of them use adequate personalization of treatment. Furthermore, none of the ongoing and currently registered trials analyzes the "ii) 20 Gy in 5 treatment sessions" versus stereotactic in the direct comparison between two single randomized arms. The aim of this randomized multicenter prospective trial study is to evaluate the pain control effectiveness of an unconventional fractionation delivered with the most innovative stereotactic technique approach available in this clinical scenario against the conventional one; enrollment of patients will be specifically selected with prognosis> 6 months according to the Mizumoto score (Mizumoto M, 2008) and structural stability defined according to Spine Instability Neoplastic Score (SINS) <7, with indication to radiotherapy on bone metastases. Highlights of this study include: the high level of treatment customization for both accurate selection and ultraconformed radiation therapy planning; the reduction in the number of sessions to which the patient must be subjected, which reduces his discomfort; the approach innovation; the location of the study group (multicentric, in the Italian panorama) in a central position in the international scenario of the specific sector. The results of this trial are potentially "practice-changing".

Conditions

Bone Metastases; Radiotherapy; Technology

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Arm A

Standard Radiotherapy: 4 Gy x 5 fractions (fr) to Whole vertebra

Group Type: NO_INTERVENTION

No interventions assigned to this group

Arm B

Intervention: Radiotherapy with Simultaneous Integrated Boost-SIB on macroscopic metastases

Delivery of a boost on macroscopic secondary lesion with Simultaneous Integrated Boost technique according this schedule:

• 5 Gy x 3 fr (Whole Vertebra) + SIB 10 Gy x 3 fr on the macroscopic disease Gross Tumor Volume - (GTV)

Group Type: EXPERIMENTAL

Simultaneous Integrated Boost-SIB on macroscopic metastases

Intervention Type: RADIATION

Delivery of a boost on macroscopic secondary lesion with Simultaneous Integrated Boost technique according this schedule:

• 5 Gy x 3 fr (Whole Vertebra) + SIB 10 Gy x 3 fr on the macroscopic disease Gross Tumor Volume - (GTV)

Interventions

Simultaneous Integrated Boost-SIB on macroscopic metastases

Delivery of a boost on macroscopic secondary lesion with Simultaneous Integrated Boost technique according this schedule:

• 5 Gy x 3 fr (Whole Vertebra) + SIB 10 Gy x 3 fr on the macroscopic disease Gross Tumor Volume - (GTV)

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Patients diagnosed with spinal bone metastases from solid, uncomplicated tumor
• Established primary or secondary tumor histology related to the treatment lesion
• Patients aged> 18 years
• Obtaining informed consent
• ECOG 0-2
• Symptomatic patients (NRS> = 4) at the treatment site
• Spine Instability Neoplastic Score (SINS) <7
• Prognosis> 6 months according to Mizumoto Prognostic Score (i.e. Class A and B)
• Spinal metastases verified at MRI including the sites to be enrolled
• No more than 3 non-contiguous spinal segments (e.g. separated by at least two metamers) involved in the study

Exclusion Criteria

• Impossibility to assign specific NRS for each CTV to be enrolled
• Impossibility to express autonomous consent to therapies
• Pregnancy
• Patient in Hospice or with prognosis <6 months
• Unavailability forecast for 3 month follow-up
• Absence of MRI pre-treatment study
• Impossibility to maintain the treatment position for SBRT
• Previous radiotherapy at the same site or at the level of adjoining metamers (higher or lower than the one to be enrolled)
• Radiometabolic therapy
• Previous enrollment of the same patient for 3 irradiated lesions
• Epidural compression of the spinal cord or of the cauda equina
• Injuries affecting> 25% of the medullary canal and / or a distance <5 mm from the medulla or from the cauda
• Injuries with indication of surgical stabilization
• Chemotherapy or target therapy within the previous 7 days and 7 days after SBRT

• Minimum Eligible Age: 18 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Dr. Cellini

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francesco Cellini, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Gemelli IRCCS - Roma

Central Contacts

Francesco Cellini, MD

Role: CONTACT

francesco.cellini@policlinicogemelli.it

+39 0630155339

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Other Identifiers

0013663/18

Identifier Type: -

Identifier Source: org_study_id