Phase II/III Study of Image-Guided Radiosurgery/SBRT for Localized Spine Metastasis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 399
- 试验地点
- 38
- 主要终点
- Percentage of Patients With Complete or Partial Pain Response at 3 Months (Phase III)
研究概览
简要总结
RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.
PURPOSE: This randomized phase II/III trial is studying how well image-guided radiosurgery or stereotactic body radiation therapy works and compares it to external-beam radiation therapy in treating patients with localized spine metastasis.
详细描述
OBJECTIVES:
Primary
- Determine the feasibility of successfully delivering image-guided radiosurgery or stereotactic body radiotherapy (SBRT) in patients with spine metastases in a cooperative group setting. (Phase II)
- Determine whether image-guided radiosurgery or SBRT (single dose of 16 Gy) improves pain control as measured by the 11-point Numerical Rating Pain Scale (NRPS) compared to conventional external beam radiotherapy (single dose of 8 Gy). (Phase III)
Secondary
- Determine whether image-guided radiosurgery or SBRT improves the rapidity of pain response and increases the duration of pain response at the treated site(s) compared to conventional external beam radiotherapy, as measured by the NRPS. (Phase III)
- Compare adverse events associated with these treatment regimens, as measured by NCI CTCAE v3.0 criteria. (Phase III)
- Evaluate the long-term effects (24 months) of image-guided radiosurgery or SBRT on the vertebral bone (e.g., compression fracture) and the spinal cord, as measured by MRI. (Phase III)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient must have localized spine metastasis from the C1 to L5 levels by a screening imaging study [bone scan, positron emission tomography (PET), computerized tomography (CT), or magnetic resonance imaging (MRI)] (a solitary spine metastasis; two separate spine levels; or up to 3 separate sites [e.g., C5, T5-6, and T12] are permitted.) Each of the separate sites may have a maximal involvement of 2 contiguous vertebral bodies. Patients can have other visceral metastasis, and radioresistant tumors (including soft tissue sarcomas, melanomas, and renal cell carcinomas) are eligible. See Figure 1 in Section 3.1.
- •of the protocol for a depiction of eligible metastatic lesions: 1) a solitary spine metastasis; 2) two contiguous spine levels involved; or 3) a maximum of 3 separate sites. Each of the separate sites may have a maximal involvement of 2 contiguous vertebral bodies. Epidural compression (arrow) is eligible when there is a ≥ 3 mm gap between the spinal cord and the edge of the epidural lesion (see #10). A paraspinal mass ≤ 5 cm is allowed (see #11).
- •There can be multiple small metastatic lesions shown in other vertebral bodies as shown in referenced diagram. The metastatic lesion of each spine should be less than 20% of the vertebral body as opposed to the diffuse vertebral involvement. These small lesions are often seen in the MRI even when bone scan or PET was negative. Most of these lesions are not clinically required to be treated and are therefore not included in the target volume of this protocol. Only the painful spine (pain score≥ 5) is to be treated .
- •Zubrod Performance Status 0-2;
- •History/physical examination within 2 weeks prior to registration;
- •Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential;
- •Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control;
- •MRI (contrast is not required but strongly recommended) of the involved spine within 4 weeks prior to registration to determine the extent of the spine involvement; an MRI is required as it is superior to a CT scan in delineating the spinal cord as well as identifying an epidural or paraspinal soft tissue component. Note: If an MRI was done as a screening imaging study for eligibility (see Section -1), the MRI can be used as the required MRI for treatment planning.
- •Numerical Rating Pain Scale within 1 week prior to registration; the patient must have a score on the Scale of ≥ 5 for at least one of the planned sites for spine radiosurgery. Documentation of the patient's initial pain score is required. Patients taking medication for pain at the time of registration are eligible.
- •Neurological examination within 1 week prior to registration to rule out rapid neurologic decline; see Appendix III for the standardized neurological examination. Patients with mild to moderate neurological signs are eligible. These neurological signs include radiculopathy, dermatomal sensory change, and muscle strength of involved extremity 4/5 (lower extremity for ambulation or upper extremity for raising arms and/or arm function).
- •Patients with epidural compression are eligible provided that there is a ≥ 3 mm gap between the spinal cord and the edge of the epidural lesion.
- •Patients with a paraspinal mass ≤ 5 cm in the greatest dimension and that is contiguous with spine metastasis are eligible.
- •Patients must provide study specific informed consent prior to study entry.
排除标准
- •Histologies of myeloma or lymphoma;
- •Non-ambulatory patients;
- •Spine instability due to a compression fracture;
- •> 50% loss of vertebral body height;
- •Frank spinal cord compression or displacement or epidural compression within 3 mm of the spinal cord;
- •Patients with rapid neurologic decline;
- •Bony retropulsion causing neurologic abnormality;
- •Prior radiation to the index spine;
- •Patients for whom an MRI of the spine is medically contraindicated;
- •Patients allergic to contrast dye used in MRIs or CT scans or who cannot be premedicated for the use of contrast dye.
研究组 & 干预措施
External Beam Radiation Therapy
干预措施: External beam radiation therapy (Radiation)
Radiosurgery/SBRT
干预措施: Radiosurgery/SBRT (Radiation)
结局指标
主要结局
Percentage of Patients With Complete or Partial Pain Response at 3 Months (Phase III)
时间窗: Baseline and 3 months
Pain is measured by the Numerical Rating Pain Scale (NRPS) a numerical 11-point scale (0-10) with 0 = no pain, 1-4 = mild, 5-6 = moderate, and 7-10 = severe with 10 the worst pain imaginable. Pain response is calculated as 3 month score - baseline score with a positive value indicating increased pain and a negative value indicating decreased pain. Patients with complete or partial pain response as defined below are considered responders. The index site is the lesion with the highest baseline (day of radiosurgery) pain score. If multiple sites have the same baseline pain score, the index site is the most cephalad lesion. * Complete response: post-treatment pain score of 0 at the index site, no increase in narcotic pain medication, and no increase in pain score at the secondary treated site(s). * Partial response: post-treatment improvement of at least 3 points at the index site, no increase in narcotic pain medication, and no increase in pain score at the secondary treated site(s).
Percentage of Patients Receiving Radiosurgery/SBRT Per Protocol or With Minor Variation (Phase II)
时间窗: The day of protocol treatment
Treatment delivery was centrally reviewed by the study chair and medical physics co-chair. Success was defined as having a review of "per protocol" or "minor variation". A 70% success rate was required for continuation to the phase III component. * Target volume compliance in is defined as the following levels of target coverage in reference to dose volume: * Per protocol: ≥ 90% * Minor variation: 80%-90% * Major deviation: \<80% of of dose volume. * Image-Guided Radiotherapy (IGRT) compliance is defined as the following differences in IGRT images between simulation/planning and treatment, as well as at the end of treatment: * Per protocol: \<2 mm * Minor variation: 2mm - 3mm * Major deviation: \> 3mm
次要结局
- Percentage of Participants With Pain Response Through Two Years (Phase III)(Baseline to two years. NRPS measured at baseline, 1, 2, and 3 weeks, 3, 6, 12, and 24 months.)
- Percentage of Participants With Pain Relapse Through Two Years (Phase III)(Randomization to two years. NRPS measured at baseline, 1, 2, and 3 weeks, 3, 6, 12, and 24 months.)
- Percentage of Patients With Adverse Events at 3 Months (Phase III)(Baseline to 3 months)
- Percentage of Participants With a Vertebral Compression Fracture Through Two Years (Phase III)(From randomization to two years.)
- Percentage of Participants With Spinal Cord Damage Through Two Years(From randomization to two years)
- Change in Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at 3 Months (Phase III)(Baseline and 3 months)
- Change in Brief Pain Inventory (BPI) Worst Pain Score Through Two Years (Phase III)(Baseline, 3, 6, 12, and 24 months)
- Change in EuroQol 5 Dimension (EQ-5D) Index Score Through Two Years (Phase III)(Baseline, 3, 6, 12, and 24 months)
- Change in Functional Assessment of Cancer Therapy - General (FACT-G) Total Score Through Two Years (Phase III)(Baseline, 3, 6, 12, and 24 months)