Comparing Radiation Therapy to Usual Care for Patients With High-Risk Bone Asymptomatic Metastases, PREEMPT Trial
Purpose
This phase III trial compares the effect of adding radiation therapy to usual care on the occurrence of bone-related complications in cancer patients with high-risk bone metastases that are not causing symptoms (asymptomatic). High-risk bone metastases are defined by their location (including hip, shoulder, long bones, and certain levels of the spine), or size (2 cm or larger). These bone metastases appear to be at higher risk of complications such as fracture, spinal cord compression, and/or pain warranting surgery or radiation treatment. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. The total dose of radiation can be delivered in a single day or divided in smaller doses for up to 5 days of total treatment. Usual care for asymptomatic bone metastases may include drugs that prevent bone loss, in addition to the treatment for the primary cancer or observation (which means no treatment until symptoms appear). Evidence has shown that preventative radiation therapy may be effective in lowering the number of bone metastases-related complications, however, it is not known if this approach is superior to usual care. Adding radiation therapy to usual care may be more effective in preventing bone-related complications than usual care alone in cancer patients with asymptomatic high-risk bone metastases.
Conditions
- Metastatic Malignant Neoplasm in the Bone
- Metastatic Malignant Solid Neoplasm
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
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) (Brief Pain Inventory [BPI] score of <
5 on the "maximum" pain item) 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
- Patients with any solid tumor type (excluding multiple myeloma)
- 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)
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Supportive Care
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm I (standard of care) |
Patients continue to receive SOC systemic anti-cancer therapy or observation and bone modifying agents as determined by the treating physician. Additionally, patients optional blood sample collection on study. |
|
|
Experimental Arm II (RT, SOC) |
Patients continue SOC as in Arm I. Patients also undergo conventional RT or SBRT QD for up to 5 days (5 fractions) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI for RT planning and optional blood sample collection on study. |
|
Recruiting Locations
Kansas City 4273837, Kansas 4273857 66160
Westwood 4281639, Kansas 4273857 66205
Kansas City 4393217, Missouri 4398678 64154
Olathe 4276614, Kansas 4273857 66061
Overland Park 4276873, Kansas 4273857 66210
Overland Park 4276873, Kansas 4273857 66211
Lee's Summit 4394870, Missouri 4398678 64064
Topeka 4280539, Kansas 4273857 66606
Site Public Contact
785-295-8000
More Details
- Status
- Recruiting
- Sponsor
- NRG Oncology
Study Contact
Detailed Description
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.