Brief Summary
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.
Brief Title
Comparing Radiation Therapy to Usual Care for Patients With High-Risk Bone Asymptomatic Metastases
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) and (b) by sex.
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) and optional blood sample collection on study.
After completion of study treatment, patients are followed up at 3, 6, 12 and 24 months.
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) and (b) by sex.
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) and optional blood sample collection on study.
After completion of study treatment, patients are followed up at 3, 6, 12 and 24 months.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Email
eringill@uw.edu
Completion Date
Completion Date Type
Estimated
Conditions
Metastatic Malignant Neoplasm in the Bone
Metastatic Malignant Solid Neoplasm
Eligibility 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 (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
* NOTE: 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)
Exclusion 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 (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
* NOTE: 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)
Exclusion Criteria:
-
Inclusion 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 (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
* NOTE: 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)
* • Patients with polymetastatic cancer defined as more than 5 sites of radiographically-evident systemic metastatic disease (excluding intracranial disease)
* "High-risk" asymptomatic bone metastasis (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
* NOTE: 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)
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06745024
Org Class
Other
Org Full Name
NRG Oncology
Org Study Id
NRG-CC014
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Radiation Therapy for High-Risk Asymptomatic Bone Metastases: A Pragmatic Multicenter Randomized Phase 3 Clinical Trial (PREEMPT)
Primary Outcomes
Outcome Description
Gray's test will be used to test for statistically significant difference in the distribution of SRE failure times (Gray 1988), accounting for death as a competing risk. The cause specific Cox proportional hazards model will be used to evaluate the treatment effect and stratification variables (Cox 1972). The analysis will be conducted on an intent-to-treat basis using all randomized patients. Analyses of treatment effect will be performed using the Cox proportional hazard model with the stratification factors as fixed covariates. The adjusted estimate of the treatment hazard ratio with a 95% confidence interval will be provided.
Outcome Measure
Incidence of skeletal-related events (SREs) (Excluding palliative radiation for pain)
Outcome Time Frame
From randomization until first SRE up to 24 months
Secondary Ids
Secondary Id
NCI-2024-08199
Secondary Outcomes
Outcome Description
OS will be compared between the two treatment arms. A stratified Cox proportional hazards model will be used to evaluate the treatment effect and stratification variables (Cox 1972). The analysis will be conducted on an intent-to-treat basis using all randomized patients. The adjusted estimate of the treatment hazard ratio with a 95% confidence interval will be provided.
Outcome Time Frame
From the time of study entry until death up to 24 months
Outcome Measure
Overall survival (OS)
Outcome Description
Hospitalization for SRE as an event will be analyzed with a logistic regression model by treatment status, adjusted for stratification factors. The adjusted estimate of the treatment odds ratio with a 95% confidence interval will be provided.
Outcome Time Frame
Up to 24 months
Outcome Measure
Hospitalizations for SRE
Outcome Description
The mean BPI scores at each collected time point (and their 95% confidence intervals) by treatment arm will be estimated. A mixed-effects model will be used to estimate and compare the mean BPI worst pain scores for the treatment arms. Model covariates will include the patients' randomly assigned study treatment, stratification factors, baseline BPI worst pain score, any opioid use, and a treatment-by-assessment time interaction term.
Outcome Time Frame
At baseline and up to 24 months
Outcome Measure
Brief Pain Inventory (BPI) scores
Outcome Description
AEs will be collected using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Descriptive statistics will be used to summarize AEs. These analyses will focus on individuals who initiated their assigned treatment and will summarize maximum grade of AEs occurring during treatment and follow-up classified by CTCAE category. The primary summary of AEs will present counts and percentages, regardless of whether the AE was attributed to any of the study agents.
Outcome Time Frame
Up to 42 days from registration (Arm I) and up to 30 days from end of treatment (Arm II)
Outcome Measure
Incidence of adverse events (AEs)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Nitin Ohri
Investigator Email
nitin.ohri@einsteinmed.edu
Investigator Phone
516-672-2711