Clinical trial NCT05534321: Prophylactic Radiotherapy of MInimally Symptomatic Spinal Disease
Official title: Prophylactic Radiotherapy of MInimally Symptomatic Spinal Disease (PROMISSeD Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Spine Metastases
Keywords: Radiotherapy (RT)
Palliative radiotherapy
High-risk asymptomatic spine metastases
Minimal asymptomatic spine metastases
Lead sponsor: Baptist Health South Florida
Sponsor class: OTHER
First posted: 2022-09-09
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Early palliative care has been shown to improve the quality of life and even survival for patients with metastatic cancer. More and more supportive oncology teams in cancer centers now advocate for early integration of radiation therapy (RT) in a patient's palliative management course. While multiple randomized studies have evaluated the efficacy of different RT regimens in the treatment of symptomatic bone lesions, few studies have examined the impact of early, upfront RT for asymptomatic or minimally symptomatic (non- opioid dependent) spine metastases and its efficacy in preventing skeletal-related events (SREs). Since the pathophysiology of spinal metastatic disease is distinct from other bony metastatic disease, the proposed trial seeks to understand whether it is beneficial to patients with minimally symptomatic disease to undergo upfront RT to reduce the risks of SREs and their sequelae, including hospitalizations.


Eligibility criteria: Inclusion Criteria:

1. Histologically-confirmed solid tumor malignancy with greater than 5 sites of metastatic disease detected on cross-sectional imaging.
2. Has high-risk bone metastases that are asymptomatic or minimally symptomatic (not requiring opioids). High risk metastases are defined as:

   1. Bulkiest sites of spinal osseous disease ≥ 2cm,
   2. Disease at junctional levels, including the thoracic apex (Occiput to C2, C7-T1, T12-L2, and L5- S1)
   3. Disease with posterior element involvement, including interspinous, unilateral, or bilateral facet joints.
   4. Vertebral body compression deformity \> 50%.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
4. Age ≥ 18 years.
5. Able to provide informed consent.
6. Patients at reproductive potential must agree to practice an effective contraceptive method. Women of childbearing potential must not be pregnant or lactating.

Exclusion Criteria:

1. Previous RT to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances.
2. Serious medical co-morbidities precluding RT.
3. Pregnant or lactating women.
4. Target lesion(s) is/are complicated bone metastases that include clinical or radiological evidence of spinal cord compression or impending pathological fracture.
5. Leptomeningeal disease.
6. Patients whose entry to the trial will cause unacceptable clinical delays in their planned management.

Primary outcomes:
measure: Number of patients who have skeletal-related events (SREs)
timeFrame: 1 year
Secondary outcomes:
measure: Number of skeletal-related event (SRE) hospitalizations
timeFrame: 1 year
measure: Pain-related quality of life
timeFrame: 3 months, 6 months, and 12 months, optionally within 1 week of a skeletal-related event (SRE)
measure: Health care utilities and quality of life
timeFrame: 3 months, 6 months, and 12 months, optionally within 1 week of a skeletal-related event (SRE)
measure: Pain-free survival (PFS)
timeFrame: Until 1 year
measure: Overall survival (OS)
timeFrame: Until 1 year
measure: Adverse event frequency and severity
timeFrame: 3 months, 6 months, and 12 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health South Florida
state: Florida
Study officials:
affiliation: Miami Cancer Institute
name: Rupesh R Kotecha, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002 Aug;2(8):584-93. doi: 10.1038/nrc867.
citation: Lutz ST, Jones J, Chow E. Role of radiation therapy in palliative care of the patient with cancer. J Clin Oncol. 2014 Sep 10;32(26):2913-9. doi: 10.1200/JCO.2014.55.1143. Epub 2014 Aug 11.
citation: Lutz S, Balboni T, Jones J, Lo S, Petit J, Rich SE, Wong R, Hahn C. Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence-Based Guideline. Pract Radiat Oncol. 2017 Jan-Feb;7(1):4-12. doi: 10.1016/j.prro.2016.08.001. Epub 2016 Aug 5.
citation: Rades D, Segedin B, Conde-Moreno AJ, Garcia R, Perpar A, Metz M, Badakhshi H, Schreiber A, Nitsche M, Hipp P, Schulze W, Adamietz IA, Norkus D, Rudat V, Cacicedo J, Schild SE. Radiotherapy With 4 Gy x 5 Versus 3 Gy x 10 for Metastatic Epidural Spinal Cord Compression: Final Results of the SCORE-2 Trial (ARO 2009/01). J Clin Oncol. 2016 Feb 20;34(6):597-602. doi: 10.1200/JCO.2015.64.0862. Epub 2016 Jan 4.
citation: Zimmermann C, Swami N, Krzyzanowska M, Hannon B, Leighl N, Oza A, Moore M, Rydall A, Rodin G, Tannock I, Donner A, Lo C. Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial. Lancet. 2014 May 17;383(9930):1721-30. doi: 10.1016/S0140-6736(13)62416-2. Epub 2014 Feb 19.
citation: Rothrock RJ, Reiner AS, Barzilai O, Kim NC, Ogilvie SQ, Lis E, Gulati A, Yamada Y, Bilsky MH, Laufer I. Responder Analysis of Pain Relief After Surgery for the Treatment of Spinal Metastatic Tumors. Neurosurgery. 2022 Oct 1;91(4):604-617. doi: 10.1227/neu.0000000000002083. Epub 2022 Jul 22.
citation: Lipton A, Theriault RL, Hortobagyi GN, Simeone J, Knight RD, Mellars K, Reitsma DJ, Heffernan M, Seaman JJ. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000 Mar 1;88(5):1082-90. doi: 10.1002/(sici)1097-0142(20000301)88:53.0.co;2-z.
citation: Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Zheng M; Zoledronic Acid Prostate Cancer Study Group. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst. 2004 Jun 2;96(11):879-82. doi: 10.1093/jnci/djh141.
citation: Rosen LS, Gordon D, Tchekmedyian NS, Yanagihara R, Hirsh V, Krzakowski M, Pawlicki M, De Souza P, Zheng M, Urbanowitz G, Reitsma D, Seaman J. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial. Cancer. 2004 Jun 15;100(12):2613-21. doi: 10.1002/cncr.20308.
citation: Saad F, Lipton A. Zoledronic acid is effective in preventing and delaying skeletal events in patients with bone metastases secondary to genitourinary cancers. BJU Int. 2005 Nov;96(7):964-9. doi: 10.1111/j.1464-410X.2005.05740.x.
citation: Duran I, Fink MG, Bahl A, Hoefeler H, Mahmood A, Luftner D, Ghazal H, Wei R, Chung KC, Hechmati G, Green J, Atchison C. Health resource utilisation associated with skeletal-related events in patients with bone metastases secondary to solid tumours: regional comparisons in an observational study. Eur J Cancer Care (Engl). 2017 Nov;26(6). doi: 10.1111/ecc.12452. Epub 2016 Feb 10.
citation: Luftner D, Lorusso V, Duran I, Hechmati G, Garzon-Rodriguez C, Ashcroft J, Bahl A, Ghelani P, Wei R, Thomas E, Hoefeler H. Health resource utilization associated with skeletal-related events in patients with advanced breast cancer: results from a prospective, multinational observational study. Springerplus. 2014 Jun 30;3:328. doi: 10.1186/2193-1801-3-328. eCollection 2014.
citation: Stopeck A, Rader M, Henry D, Danese M, Halperin M, Cong Z, Qian Y, Dansey R, Chung K. Cost-effectiveness of denosumab vs zoledronic acid for prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States. J Med Econ. 2012;15(4):712-23. doi: 10.3111/13696998.2012.675380. Epub 2012 Mar 27.
citation: Degen JW, Gagnon GJ, Voyadzis JM, McRae DA, Lunsden M, Dieterich S, Molzahn I, Henderson FC. CyberKnife stereotactic radiosurgical treatment of spinal tumors for pain control and quality of life. J Neurosurg Spine. 2005 May;2(5):540-9. doi: 10.3171/spi.2005.2.5.0540.
citation: Daut RL, Cleeland CS, Flanery RC. Development of the Wisconsin Brief Pain Questionnaire to assess pain in cancer and other diseases. Pain. 1983 Oct;17(2):197-210. doi: 10.1016/0304-3959(83)90143-4.
citation: Jensen MP, Turner JA, Romano JM, Fisher LD. Comparative reliability and validity of chronic pain intensity measures. Pain. 1999 Nov;83(2):157-62. doi: 10.1016/s0304-3959(99)00101-3.
citation: Cleeland CS. Measurement of pain by subjective report. In: Chapman CR; Loeser JD, editors. Issues in pain measurement. New York: Raven Press; 1989: 391-403.
citation: Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, Silberman M, Yellen SB, Winicour P, Brannon J, et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol. 1993 Mar;11(3):570-9. doi: 10.1200/JCO.1993.11.3.570.
citation: Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001 Jul;33(5):337-43. doi: 10.3109/07853890109002087.
citation: Badia X, Herdman M, Kind P. The influence of ill-health experience on the valuation of health. Pharmacoeconomics. 1998 Jun;13(6):687-96. doi: 10.2165/00019053-199813060-00005.
citation: Mirels H. Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res. 1989 Dec;(249):256-64.