Reduction of Pain Symptoms With Stereotactic Radiotherapy on Bone Metastases

NCT03597984 | Unknown

• 1 other identifier: 0013663/18
• Study Type: interventional
• Target: 330
• Locations: 0 countries
• Sites: N/A

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)

Conditions

Bone Metastases; Radiotherapy; Technology

Outcome Measures

Primary Outcomes (1)

• Pain control [EFFICACY and PAIN]

  Pain control measured with Numeric Rating Scale (NRS) score, a 11-point scale for patient self-reporting of pain. NRS score presents a total range between 0 (no pain) and 10 maximum pain. NRS subscale are the sequent: * 0: no pain \[better outcome \] * 1-3: mild pain * 4-6: moderate pain * 7-10 severe pain \[worse outcome\]

  3 months

Secondary Outcomes (7)

• Pain control duration [EFFICACY and PAIN]

  12 months after end of radiotherapy

• Local control [EFFICACY]

  At 3, 6 and 12 months from the end of radiotherapy

• Symptom Progression Free Survival (SPFS) [EFFICACY and PAIN]

  12 months after end of radiotherapy

• Progression-free survival - PFS [EFFICACY]

  12 months

• Overall survival [EFFICACY]

  12 months

Study Arms (2)

Arm A

NO INTERVENTION

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

Arm B

EXPERIMENTAL

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)

Radiation: Simultaneous Integrated Boost-SIB on macroscopic metastases

Interventions

Simultaneous Integrated Boost-SIB on macroscopic metastases 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)

Arm B

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Related Publications (13)

• 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, Tome 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. doi: 10.1118/1.3438081.

  PMID: 20879569 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Ryu S, Pugh SL, Gerszten PC, Yin FF, Timmerman RD, Hitchcock YJ, Movsas B, Kanner AA, Berk LB, Followill DS, Kachnic LA. RTOG 0631 phase 2/3 study of image guided stereotactic radiosurgery for localized (1-3) spine metastases: phase 2 results. Pract Radiat Oncol. 2014 Mar-Apr;4(2):76-81. doi: 10.1016/j.prro.2013.05.001. Epub 2013 Jun 4.

  PMID: 24890347 RESULT

• van der Velden JM, Verkooijen HM, Seravalli E, Hes J, Gerlich AS, Kasperts N, Eppinga WS, Verlaan JJ, van Vulpen M. Comparing conVEntional RadioTherapy with stereotactIC body radiotherapy in patients with spinAL metastases: study protocol for an randomized controlled trial following the cohort multiple randomized controlled trial design. BMC Cancer. 2016 Nov 21;16(1):909. doi: 10.1186/s12885-016-2947-0.

  PMID: 27871280 RESULT

• Cellini F, Manfrida S, Deodato F, Cilla S, Maranzano E, Pergolizzi S, Arcidiacono F, Di Franco R, Pastore F, Muto M, Borzillo V, Donati CM, Siepe G, Parisi S, Salatino A, D'Agostino A, Montesi G, Santacaterina A, Fusco V, Santarelli M, Gambacorta MA, Corvo R, Morganti AG, Masiello V, Muto P, Valentini V. Pain REduction with bone metastases STereotactic radiotherapy (PREST): A phase III randomized multicentric trial. Trials. 2019 Oct 28;20(1):609. doi: 10.1186/s13063-019-3676-x.

  PMID: 31661034 DERIVED

Study Officials

• Francesco Cellini, MD

  Fondazione Policlinico Gemelli IRCCS - Roma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Francesco Cellini, MD

CONTACT

+39 0630155339; francesco.cellini@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: For each patient the following variables for balancing the study arms will be considered: Gender, age, performance status, histology, site and primary tumor and presence of visceral metastases; Randomization will be performed at the Gemelli ART of the Gemelli Polyclinic Foundation and will be done by e-mail. Patients will be randomized after verification of inclusion and exclusion criteria. Randomization will be performed according to a random list generated by the computer.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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%.

Study Record Dates

• First Submitted: May 31, 2018
• First Posted: July 24, 2018
• Study Start: July 1, 2019
• Primary Completion: July 1, 2019
• Study Completion: December 28, 2020
• Last Updated: July 5, 2019

Record last verified: 2019-07