Prophylactic Radiotherapy of MInimally Symptomatic Spinal Disease

Official title

Prophylactic Radiotherapy of MInimally Symptomatic Spinal Disease (PROMISSeD Trial)

Overview

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.

Interventions

• Radiation Prophylactic Radiotherapy
  Radiation therapy will be delivered according to department standards. For this protocol, total dose and dose fractionation may be delivered at the discretion of the treating radiation oncologist according to department standards. All techniques including conventional, three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and stereotactic radiosurgery/stereotactic body radiation therapy (SRS/SBRT) techniques may be used. Image guidance at the time
• Drug Standard of care systemic therapy
  Standard of care systemic therapy, including chemotherapeutics, targeted therapies, immunomodulatory agents, and hormonal therapies will be delivered at the discretion of the treating medical oncologist. Patients may receive systemic therapy concurrently and there are no restrictions on initiation of systemic agents after radiotherapy including immunotherapy and hormonal therapy, the timing of which will be determined by a consensus between the treating medical and radiation oncologists.

Primary outcome measures

• Number of patients who have skeletal-related events (SREs) [Time frame: 1 year]

Secondary outcome measures (6)

• Number of skeletal-related event (SRE) hospitalizations [Time frame: 1 year]
• Pain-related quality of life [Time frame: 3 months, 6 months, and 12 months, optionally within 1 week of a skeletal-related event (SRE)]
• Health care utilities and quality of life [Time frame: 3 months, 6 months, and 12 months, optionally within 1 week of a skeletal-related event (SRE)]
• Pain-free survival (PFS) [Time frame: Until 1 year]
• Overall survival (OS) [Time frame: Until 1 year]
• Adverse event frequency and severity [Time frame: 3 months, 6 months, and 12 months]

Eligibility criteria

Inclusion criteria

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

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

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Supportive care

Study locations

United States · 1 center

• Miami Cancer Institute at Baptist Health South Florida — Miami

Publications

• Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002 Aug;2(8):584-93. doi: 10.1038/nrc867. PMID 12154351
• 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. PMID 25113773
• 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. PMID 27663933
• 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 PMID 26729431
• 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. PMID 24559581
• 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. PMID 35856981
• 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.c PMID 10699899
• 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. PMID 15173273

Identifiers

NCT: NCT05534321 · 2021-KOT-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗