Study of Palliative Radiation Therapy vs. no Palliative Radiation Therapy for Patients With High Risk Bone Metastases That Are Not Causing Significant Pain

Study Overview
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Brief Summary
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The purpose of the study is to compare the outcome of patients who receive standard treatment versus those who receive preventative radiation and then standard treatment.

Official Title
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A Randomized Trial of Early, Upfront Palliative Radiation Therapy Versus Standard of Care for Patients With Highest Risk Asymptomatic or Minimally Symptomatic Bone Metastases

Conditions
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Metastatic Solid Tumors of Metastatic Disease

Intervention / Treatment
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* Radiation: Radiation Therapy
* Drug: Systemic Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed solid tumor malignancy with greater than 5 sites of metastatic disease detected on imaging. Has high risk bone metastases that are asymptomatic or minimally symptomatic (not requiring opioids). High risks metastases are defined as: 1. bulkiest sites of osseous disease ≥ 2cm, 2. disease involving the hip (acetabulum, femoral head, femoral neck), shoulder (acromion, glenoid, humeral head), or sacroiliac joints 3. disease in long bones with1/3-2/3 cortical thickness (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpus, phalanges) 4. disease in junctional spine (C7-T1, T12-L1, L5-S1) and/or disease with posterior element involvement. 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 radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances. Serious medical co-morbidities precluding radiotherapy. 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. Malignant pleural effusion. Absolute neutrophil count (ANC) <1.0 K/mcL and platelet count <50 K/mcL at time of enrollment. Patients whose entry to the trial will cause unacceptable clinical delays in their planned management.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In this trial patients will be divided into 2 cohorts. Patients in Cohort 1 will undergo standard of care therapy for bone metastases. Patients in Cohort 2 will undergo upfront RT to ≤5 highest risk bone metastases first followed by standard of care therapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of care<br>Patients randomized to Arm 1 will undergo appropriate therapy as determined by their oncologist. These patients will either continue their current therapy or be transitioned to a new standard of care therapy at the discretion of the treating oncologist. If randomized to Arm 1, these patients may undergo palliative RT for progressive, painful lesions (a skeletal related event) at time of symptom development (not upfront palliative RT). | Drug: Systemic Therapy<br>* 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.<br>|
| Experimental: Selective radiation to ≤5 highest risk bone metastases<br>Patients on Arm 2 of the study will undergo selective RT to ≤ 5 high risk bone metastases defined as 1. bulkiest sites of osseous disease ≥ 2cm, 2. disease involving the hip (acetabulum, femoral head, femoral neck), shoulder (acromion, glenoid, humeral head), or sacroiliac joints 3. disease in long bones with1/3-2/3 cortical thickness (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpus, phalanges) 4. disease in junctional spine (C7-T1, T12-L1, L5-S1) &/or disease with posterior element involvement. | Radiation: Radiation Therapy<br>* 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, 3D-CRT, or IMRT technique may be used. Image guidance at the time of treatment delivery to verify patient positioning may be chosen at the discretion of the treating radiation oncologist according to department standards.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients who have skeletal related events (SREs) | which will be defined as pathological fractures, spinal cord compression, or palliative radiotherapy and orthopedic surgery to bone. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palliative Radiation, 18-196