Comparing Radiation Therapy to Usual Treatment for Patients With High-Risk Bone Metastases That Are Not Causing Pain, PREEMPT Trial

PRIMARY OBJECTIVE:

I. To determine whether prophylactic radiation therapy (RT) to high-risk asymptomatic bone metastases decreases the occurrence of skeletal-related events (SREs), including pathologic fracture, spinal cord compression, and surgery to bone (not including palliative radiation for pain only), compared to standard of care (SOC).

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) between study arms. II. To compare occurrence of any SREs (including RT for palliation of pain) among enrolled bone metastasis(es) between study arms.

III. To compare occurrence of hospitalizations related to any SREs in enrolled bone metastasis(es) between study arms.

IV. To compare pain-related quality of life (QOL) between study arms. V. To characterize adverse events of RT and compare to SOC.

EXPLORATORY OBJECTIVES:

I. To evaluate overall QOL, functional status, and quality-adjusted life years between study arms.

II. To evaluate any hospitalizations (from any cause) between study arms. III. To characterize differences in primary and secondary endpoints between study arms (a) among the represented racial and ethnic groups (e.g. Black, White, Hispanic/Latino, Asian/Pacific Islander, and Native American), (b) by sex, and (c) by health-related social needs.

IV. To evaluate the heterogeneity of radiation treatment effect based on cancer-related factors (histology, criteria indicating high-risk for SRE), treatment-related factors (bone modifying agent use, radiation dose/technique), and patient demographic factors (age, sex, race, ethnicity, and health-related social needs).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients continue to receive SOC systemic anti-cancer therapy or observation and bone modifying agents as determined by the treating physician. Additionally, patients undergo optional blood sample collection on study.

ARM II: Patients continue SOC as in Arm I. Patients also undergo conventional RT or stereotactic body radiation therapy (SBRT) once daily (QD) for up to 5 days (5 fractions) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) for RT planning and optional blood sample collection on study.

After completion of study treatment, patients are followed up at 3, 6, 12 and 24 months.

Inclusion criteria

• Patients with polymetastatic cancer defined as more than 5 sites of radiographically-evident systemic metastatic disease (excluding intracranial disease)
• "High-risk" asymptomatic bone metastasis(es) (defined as pain score of < 5 on a 0-10 scale using question #3 from the Brief Pain Inventory [BPI]) defined as fulfilling at least one of the following four high-risk criteria:

• Bulky site of disease in bone (>= 2 cm);
• Disease involving the hip (acetabulum, femoral head, femoral neck), shoulder (acromion, glenoid, humeral head), or sacroiliac joints;
• Disease in long bones occupying up to 2/3 of the cortical thickness (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpals, phalanges); and/or
• Disease in junctional spine (C7-T1, T12-L1, L5-S1) and/or disease with posterolateral element (pedicles and/or facet joints) involvement.

NOTES:

• Patients may have up to 3 individual high-risk bone metastases enrolled in the study. Sternum, rib, and scapula are defined as flat bones so lesions in these locations would only be included if bulky (per high-risk criteria #1)
• Question #3 from the Brief Pain Inventory (BPI): "On a scale of 0-10, 0 being no or least amount of pain, and 10 being the worst pain imaginable, what score would you rate your worst pain in the last 24 hours."

• The pain score can be lesion-specific and does not need to refer to overall pain.
• The remaining questions on the BPI are not required to confirm eligibility

• Patients with any solid tumor type (excluding multiple myeloma and lymphoma)
• Patients must have systemic disease evaluation through standard of care diagnostic imaging, including either CT chest/abdomen/pelvis or body positron emission tomography (PET)/CT, with radiology report available
• Patients with treated brain metastases and no known leptomeningeal disease are eligible if these lesions have been treated prior to enrollment
• Age ≥ 18
• Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky performance status (KPS) ≥ 60
• No previous radiotherapy to the intended enrolled sites of disease
• No epidural spinal cord compression (ESCC) ≥ grade 1c (defined as deformation of the thecal sac with spinal cord abutment) at the enrolled bone metastasis(es)
• No prior fracture at the enrolled bone metastasis(es)