SAINT: Single frActIoN eighT Gray Palliative Radiotherapy With Modulated Intensity for Pain Reduction: a Single Arm Cohort Analysis

Single frActIoN eighT Gray Palliative Radiotherapy With Modulated Intensity for Pain Reduction



Sponsors


Source

Policlinico Universitario Agostino Gemelli

Oversight Info

Has Dmc

No

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


Brief Summary

Non-randomized, monocentric, observational study to evaluate the response in terms of
reduction of painful symptoms from bone metastases to radiotherapy with high personalization
of treatment: performed with modern technology, supplied with modulated intensity technique
with concomitant integrated boost, according to selection of patients in accordance with
prognosis determined by specific prognostic score

Detailed Description

Palliative antalgic oncological treatments concern a chronically-evolving disease patient
with pain control problems, and are a complex problem from different points of view:
logistic, clinical and scientific research. An increasing number of patients are afflicted
due to the increased incidence of cancer in all its phases and the potential chronicity of
the disease linked to new therapies.

The use of palliative anti-radiation radiotherapy treatments involves up to 40% of patients
in a Radiotherapy Center. Radiotherapy was used in the palliative treatment of symptomatic
bone metastases to improve quality of life (QoL) of these patients. This is the easiest way
to respond to problems of home care or long-term care (eg: Hospice). This need is
particularly accentuated for patients with a more severe situation. To reduce the overall
duration of the treatment, it is necessary to manage hypofractionated regulators (ie with
dose fractionation which daily dispense a dose higher than 2Gy). In fact, hypofractionated
regimes concern the gold standard for these clinical presentations.

With the same pain control, multiple fractionation boards report better symptom control over
time and are therefore very often preferred for patients with a prognosis> 6 months. On the
other hand, the treatment regimen with 8 Gy in single therapy session is suggested as
preferable for patients with a worse prognosis (ie less than 6 months of life expectancy).
Evidence from literature suggests that palliative radiation therapy is effective in
controlling pain even in the last weeks of the patient's life and therefore useful to improve
the conditions of patients with a more severe prognosis.

The identification of patients with the worst prognosis to which single-agent radiotherapy is
reserved is another crucial aspect. Unfortunately, although clinically validated in
scientific trials, the routine use of prognostic scores is rarely used in everyday clinical
practice to characterize life expectancy and define the most appropriate treatment regimen.
This aspect limits the effective personalization of palliative treatments of this type.

Furthermore, the indications available in the literature do not specify a univocally shared
standard of technical approach to radiant treatment. The Consensus Conference whose data have
been reported by Chow et al. considers as potentially applicable both non-conformed
techniques (e.g .: single back beam) and the most modern conformational techniques. The less
conformed techniques have the defect of distributing in a more variable way the dose inside
the target to irradiate and to save less well the organs at risk (OAR) with consequent
increase of the risk of toxicity that could reduce the beneficial to the patient given by the
reduction of pain from metastases.

Finally, the prescription of the single 8 Gy radiotherapy session in daily practice is still
not sufficiently widespread, as evidenced by international literature . 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.

This particular analysis, within the Umbrella Protocol, focuses on patients with
uncomplicated and painful vertebral bone metastases, and is aimed at observing and recording
the efficacy of treatment in a single 8 Gy session, applied in good clinical practice.
according to available evidence.

Particular attention is paid to applying a high degree of personalization of the treatment
and a modern approach to the technology of performing the radiant treatment. The
personalization of the treatment will be favored by the routine use of: i) a valid prognostic
score for the expected survival, the Mizumoto prognostic Score (Mizumoto M, 2008), to
identify patients with the worst prognosis to offer treatment in a single session. The use of
the most advanced radiation dose administration technologies will be applied by choosing (in
the spectrum of technologies applicable to these clinical presentations) the most modern
modulated intensity radiotherapy (IMRT). IMRT allows to reduce the dose administered to the
OAR and to concentrate the areas with the highest dose concentration (the so-called "hot
spots") only within the evidence of disease (or "Gross tumor Volume" - GTV). Through the
integrated simultaneous boost (SIB) method in IMRT, it is possible, in fact, to check the
extent and location of the "hot zones" by specifying, through precise prescription, the
maximum desired amount and the topographic limits to the inside of the target prescribed at
the dose of 8 Gy, however doing "drop" the dose to the surrounding OAR.

The hypothesis of the study is to observe the rates of pain control and the need to retract
the patient, when applied to personalization of indications and maximum technological
support. These results could be a basis of scientific evidence to further support the
clinical orientation towards the use of the single fraction of radiotherapy with consequent
improvement in the quality of life of these patients. Furthermore, such data will be able to
feed further analyzes aimed at the cost / effectiveness of this approach.

Overall Status

Not yet recruiting

Start Date

2018-08-01

Completion Date

2019-07-31

Primary Completion Date

2018-12-31

Study Type

Observational [Patient Registry]

Primary Outcome

Measure

Time Frame

Pain control
1 month after end of radiotherapy

Secondary Outcome

Measure

Time Frame

Re-treatment during follow up
12 months after end of radiotherapy
Pain-dipendent variables
12 months after end of radiotherapy

Enrollment

50

Conditions


Intervention

Intervention Type

Other

Intervention Name


Description

Observe the rates of pain control and the need to retreat patient, when applied to personalization of indications and maximum technological support for palliative radiotherapy to patients with < 6 months prognostic score attendance


Eligibility

Study Pop

Considering the observational nature of the study, all patients corresponding to the
"Inclusion Criteria" will be taken into consideration over a period of 6 months from the
beginning of the study. 50 patients are expected to be enrolled.

Sampling Method

Non-Probability Sample

Criteria

Inclusion Criteria:

- Patients diagnosed with spinal bone metastases from solid, uncomplicated tumor

- Established primary or secondary tumor histology correlated to the treatment lesion

- Age >18 years

- Obtaining informed consent

- Symptomatic patients (NRS> = 4) at the treatment site

- Prognosis <6 months according to Mizumoto Prognostic Score (i.e. Class B or C)

- Spine Instability Neoplastic Score (SINS) <7

Exclusion Criteria:

- Concurrent disorders (psychiatric and otherwise) which, in the opinion of the
investigator, make data collection unreliable

- Impossibility to assign specific NRS for each CTV to be enrolled

- 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

- Pregnancy

Gender

All

Minimum Age

18 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Francesco Cellini, MD
Principal Investigator
Fondazione Policlinico Gemelli IRCCS - Roma

Overall Contact

Last Name

Francesco Cellini, MD

Phone

+39 0630155339

Email



Verification Date

2018-07-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

Policlinico Universitario Agostino Gemelli

Investigator Full Name

Dr. Cellini

Investigator Title

Principal Investigator


Has Expanded Access

No

Results Reference

Citation

Benedict SH, Yenice KM, Followill D, Galvin JM, Hinson W, Kavanagh B, Keall P, Lovelock M, Meeks S, Papiez L, Purdie T, Sadagopan R, Schell MC, Salter B, Schlesinger DJ, Shiu AS, Solberg T, Song DY, Stieber V, Timmerman R, Tomé WA, Verellen D, Wang L, Yin FF. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010 Aug;37(8):4078-101. Erratum in: Med Phys. 2012 Jan;39(1):563. Dosage error in article text.

PMID

20879569


Citation

Bentzen SM, Constine LS, Deasy JO, Eisbruch A, Jackson A, Marks LB, Ten Haken RK, Yorke ED. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S3-9. doi: 10.1016/j.ijrobp.2009.09.040.

PMID

20171515


Citation

Braam P, Lambin P, Bussink J. Stereotactic versus conventional radiotherapy for pain reduction and quality of life in spinal metastases: study protocol for a randomized controlled trial. Trials. 2016 Feb 2;17:61. doi: 10.1186/s13063-016-1178-7.

PMID

26829933


Citation

Chow E, Hoskin P, Mitera G, Zeng L, Lutz S, Roos D, Hahn C, van der Linden Y, Hartsell W, Kumar E; International Bone Metastases Consensus Working Party. Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):1730-7. doi: 10.1016/j.ijrobp.2011.02.008. Epub 2011 Apr 12.

PMID

21489705


Citation

Correa RJ, Salama JK, Milano MT, Palma DA. Stereotactic Body Radiotherapy for Oligometastasis: Opportunities for Biology to Guide Clinical Management. Cancer J. 2016 Jul-Aug;22(4):247-56. doi: 10.1097/PPO.0000000000000202.

PMID

27441744


Citation

Deodato F, Cilla S, Macchia G, Torre G, Caravatta L, Mariano G, Mignogna S, Ferro M, Mattiucci GC, Balducci M, Frascino V, Piermattei A, Ferrandina G, Valentini V, Morganti AG. Stereotactic radiosurgery (SRS) with volumetric modulated arc therapy (VMAT): interim results of a multi-arm phase I trial (DESTROY-2). Clin Oncol (R Coll Radiol). 2014 Dec;26(12):748-56. doi: 10.1016/j.clon.2014.08.005. Epub 2014 Aug 29.

PMID

25175042


Citation

Furfari A, Wan BA, Ding K, Wong A, Zhu L, Bezjak A, Wong R, Wilson CF, DeAngelis C, Azad A, Chow E, Charames GS. Genetic biomarkers associated with pain flare and dexamethasone response following palliative radiotherapy in patients with painful bone metastases. Ann Palliat Med. 2017 Dec;6(Suppl 2):S240-S247. doi: 10.21037/apm.2017.09.04. Epub 2017 Sep 20.

PMID

29156912


Citation

Guckenberger M, Hawkins M, Flentje M, Sweeney RA. Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial. BMC Cancer. 2012 Nov 19;12:530. doi: 10.1186/1471-2407-12-530.

PMID

23164174


Citation

Mizumoto M, Harada H, Asakura H, Hashimoto T, Furutani K, Hashii H, Takagi T, Katagiri H, Takahashi M, Nishimura T. Prognostic factors and a scoring system for survival after radiotherapy for metastases to the spinal column: a review of 544 patients at Shizuoka Cancer Center Hospital. Cancer. 2008 Nov 15;113(10):2816-22. doi: 10.1002/cncr.23888.

PMID

18846565


Citation

Murai T, Murata R, Manabe Y, Sugie C, Tamura T, Ito H, Miyoshi Y, Shibamoto Y. Intensity modulated stereotactic body radiation therapy for single or multiple vertebral metastases with spinal cord compression. Pract Radiat Oncol. 2014 Nov-Dec;4(6):e231-7. doi: 10.1016/j.prro.2014.02.005. Epub 2014 Mar 31.

PMID

25407874


Citation

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PMID

24890347


Citation

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PMID

27871280



Firstreceived Results Date

N/A

Acronym

SAINT

Target Duration

12 Months

Patient Data

Sharing Ipd

Undecided


Firstreceived Results Disposition Date

N/A

Study Design Info

Observational Model

Cohort

Time Perspective

Prospective


Study First Submitted

May 31, 2018

Study First Submitted Qc

May 31, 2018

Study First Posted

June 12, 2018

Last Update Submitted

July 3, 2018

Last Update Submitted Qc

July 3, 2018

Last Update Posted

July 6, 2018


ClinicalTrials.gov processed this data on July 06, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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