Clinical trial NCT03597984: Reduction of Pain Symptoms With Stereotactic Radiotherapy on Bone Metastases
Official title: PREST: Pain REduction With Bone Metastases STereotactic Radiotherapy: A Phase III Randomized Multicentric Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Bone Metastases
Radiotherapy
Technology
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2018-07-24
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is a randomized, controlled superiority trial. The study will appear as an interventionist without medicinal, multicentric, spontaneous. Randomization will take place in a 1: 1 ratio. The study involves the enrollment of 330 patients divided into two groups of 165 patients for each of the two study arms (arm A (gold standard): 4 Gy x 5 fractions (fr); arm B: 5 Gy x 3 fr (Whole Vertebra) + SIB 10 Gy x 3 fr on the Gross Tumor Volume - GTV). The expected difference between the two treatments in terms of three-month pain control rates is 15% more in the experimental arm compared to the standard arm.

The calculation of the sample size took into account a 95% CI with a coefficient α of 0.05 and a drop-out rate of 10%.
Primary purpose: TREATMENT

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".

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

Primary outcomes:
measure: Pain control [EFFICACY and PAIN]
timeFrame: 3 months
Secondary outcomes:
measure: Pain control duration [EFFICACY and PAIN]
timeFrame: 12 months after end of radiotherapy
measure: Local control [EFFICACY]
timeFrame: At 3, 6 and 12 months from the end of radiotherapy
measure: Symptom Progression Free Survival (SPFS) [EFFICACY and PAIN]
timeFrame: 12 months after end of radiotherapy
measure: Progression-free survival - PFS [EFFICACY]
timeFrame: 12 months
measure: Overall survival [EFFICACY]
timeFrame: 12 months
measure: Quality of Life (QoL) [EFFICACY and QUALITY OF LIFE]
timeFrame: At first visit, 1 month and 3 months after the end of radiotherapy
measure: Rate of retreatments [EFFICACY]
timeFrame: 12 months after end of radiotherapy
Other outcomes:
Locations:
Study officials:
affiliation: Fondazione Policlinico Gemelli IRCCS - Roma
name: Francesco Cellini, MD
role: PRINCIPAL_INVESTIGATOR
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