Radiation Therapy for High-Risk Asymptomatic Bone Metastases: A Pragmatic Multicenter Randomized Phase 3 Clinical Trial (PREEMPT)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- NRG Oncology
- 入组人数
- 280
- 试验地点
- 1,015
- 主要终点
- Incidence of skeletal-related events (SREs) (Excluding palliative radiation for pain)
研究概览
简要总结
This phase III trial compares the effect of adding radiation therapy to usual treatment on the occurrence of bone-related complications in cancer patients with high-risk bone metastases that are not causing symptoms, such as pain (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 treatment 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 treatment may be more effective in preventing bone-related complications than usual care alone in cancer patients with asymptomatic high-risk bone metastases.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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
- •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)
排除标准
- 未提供
研究组 & 干预措施
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 undergo optional blood sample collection on study.
干预措施: Biospecimen Collection (Procedure)
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 undergo optional blood sample collection on study.
干预措施: Bone Metastases Treatment (Other)
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 undergo optional blood sample collection on study.
干预措施: Patient Observation (Other)
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 undergo optional blood sample collection on study.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Best Practice (Other)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Bone Metastases Treatment (Other)
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.
干预措施: Computed Tomography (Procedure)
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.
干预措施: Conventional Radiotherapy (Procedure)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
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.
干预措施: Patient Observation (Other)
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Stereotactic Body Radiation Therapy (Radiation)
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 undergo optional blood sample collection on study.
干预措施: Best Practice (Other)
结局指标
主要结局
Incidence of skeletal-related events (SREs) (Excluding palliative radiation for pain)
时间窗: From randomization until first SRE up to 24 months
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.
次要结局
- Overall survival (OS)(From the time of study entry until death up to 24 months)
- Hospitalizations for SRE(Up to 24 months)
- Brief Pain Inventory (BPI) scores(At baseline and up to 24 months)
- Incidence of adverse events (AEs)(Up to 42 days from registration (Arm I) and up to 30 days from end of treatment (Arm II))