Prophylactic Radiotherapy of MInimally Symptomatic Spinal Disease

Phase 1

Recruiting

• Conditions: Spine Metastases
• Interventions: Radiation: Prophylactic Radiotherapy; Drug: Standard of care systemic therapy

• Registration Number: NCT05534321
• Lead Sponsor: Baptist Health South Florida

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-08-29
• Study First Submitted: 2022-09-06
• Study First Submitted QC: 2022-09-06
• Study First Posted: 2022-09-09
• Status Verified: 2025-01
• Last Update Submitted: 2025-02-05
• Last Update Posted: 2025-02-06
• Primary Completion: 2026-09
• Study Completion: 2027-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 74

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prophylactic Radiation Therapy	Prophylactic Radiotherapy	Patients randomized to Arm 2 of the study will undergo upfront prophylactic radiotherapy to ≤ 5 highest risk bone metastases followed by standard of care, as defined by: 1. Bulkiest sites of disease ≥ 2cm (can include paraspinal disease extension) 2. Disease in junctional spine (Occ-C2, C7-T1, T12-L1, L5-S1) 3. Disease with posterior element involvement (facet(s), interspinous) 4. Compression Deformity \> 50%
Standard of Care Systemic Therapy or Surveillance	Standard of care systemic therapy	Patients randomized to arm 1 will undergo appropriate systemic therapy as determined by their oncology team. These patients will either continue the 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 also undergo palliative radiation therapy for progressive or painful lesions (a skeletal related event as defined in the study) at the time of symptom development\*(not upfront palliative radiation therapy)

Primary Outcome Measures

Name	Time	Method
Number of patients who have skeletal-related events (SREs)	1 year	Number of skeletal related events (SREs), which will be defined as pathological fractures, spinal cord compression, or interventions (palliative RT, interventional procedures, or spine surgery)

Secondary Outcome Measures

Name	Time	Method
Pain-free survival (PFS)	Until 1 year	Pain-free survival (PFS) is defined as the time from study entry to until the start of opioid use or until death.
Pain-related quality of life	3 months, 6 months, and 12 months, optionally within 1 week of a skeletal-related event (SRE)	Pain-related quality of life using the Brief Pain Inventory (BPI) form. The BPI is a 17-item patient self-rating scale assessing demographic data, use of medications, as well as the sensory and reactive components of pain. The scale is from 0-10, and there are breakpoints between scores of 4 and 5 and between 6 and 7, indicating that mild pain correlates with scores of 1-4, moderate pain with 5-6, and severe pain with scores of 7-10.
Overall survival (OS)	Until 1 year	Overall survival (OS) is defined as the time from study entry until death.
Health care utilities and quality of life	3 months, 6 months, and 12 months, optionally within 1 week of a skeletal-related event (SRE)	Health care utilities and quality of life using the EuroQol Group EQ-5D-5L form. It has been developed to generate a generic cardinal index of health, thus giving it considerable potential for future use in economic evaluation. The EQ-5D-5L is a two-part, patient-completed questionnaire. The first part consists of 5 items covering 5 dimensions including: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on 3 levels including: 1=no problems; 2= moderate problems; and 3=extreme problems. The second component is the visual analog scale, where the participant rates their own overall health on a scale of 0 (worst health) to 100 (best health).
Adverse event frequency and severity	3 months, 6 months, and 12 months	Evaluate CTCAE v5 toxicity events in the upfront RT arm by tabulating all toxicities and summarizing the CTCAE v5 scores.
Number of skeletal-related event (SRE) hospitalizations	1 year	Number of hospitalizations attributed to skeletal-related events (SREs)

Trial Locations

Locations (1)

Miami Cancer Institute at Baptist Health South Florida; 🇺🇸 Miami, Florida, United States