Testing Short-Course Radiation Versus Standard-Course Radiation for Soft Tissue Sarcomas That Need Surgery and Radiation
Phase III Randomized Study Testing Non-Inferiority of Short-Course Ultra-Hypofractionated Radiation (UHRT-5) Versus Standard Fractionation (RT-25) for Stage II-IIIB, Extremity, Resectable Soft Tissue Sarcoma
研究概览
地位
条件
详细说明
PRIMARY OBJECTIVE:
I. To evaluate whether the incidence of local tumor recurrence at 2-years after randomization with short-course radiation is non-inferior to standard-course radiation among participants with high-risk, resectable soft tissue sarcoma.
SECONDARY OBJECTIVES:
I. To estimate and compare between arms the incidence of acute wound complications.
II. To estimate and compare between arms the incidence of late-term complications associated with radiation at 2-years post-surgery.
III. To estimate and compare between arms changes in physician-assessed functional outcome from pre-randomization to 12 and 24 months post surgery using the Musculoskeletal Tumor Society Scoring system.
IV. To estimate and compare between arms overall survival, progression-free survival, and distant-metastasis-free survival measured from randomization.
EXPLORATORY OBJECTIVES:
I. To estimate and compare between arms the incidence of local tumor recurrence at 2 years using a per-protocol analysis.
II. To estimate and compare between arms the incidence of delayed wound healing.
III. To report the type of surgical resection by treatment arm, including limb-salvage versus amputation and margin status (R0, R1, or R2).
IV. To describe the use of supportive therapy medications given with radiation therapy separately by treatment arm.
V. To describe the use of adjuvant therapy post-surgery separately by treatment arm.
BANKING OBJECTIVE:
I. To bank tissue specimens for future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients undergo RT-25 with 3D CRT or IMRT once daily (QD) for up to 5 fractions per week for 25 fractions over a minimum of 32 calendar days and maximum of 49 days in the absence of disease progression or unacceptable toxicity. Starting 22-56 calendar days after radiation, patients undergo surgical resection. Additionally, patients undergo magnetic resonance imaging (MRI), computed tomography (CT), and blood sample collection throughout the study.
ARM 2: Patients undergo UHRT-5 with 3D CRT or IMRT QD for up to 5 fractions per week for 5 fractions over a minimum of 5 calendar days and maximum of 14 days in the absence of disease progression or unacceptable toxicity. Starting 22-56 calendar days after radiation, patients undergo surgical resection. Additionally, patients undergo MRI, CT, and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 4 months, every 6 months after surgery for up to 5 years, and then annually for up to 10 years after randomization.
研究类型
注册 (估计的)
阶段
- 第三阶段
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
Participants must have histological evidence of a soft tissue sarcoma from core or incisional biopsy. Participants must have a primary or locally recurrent tumor. Stage II-IIIB (by American Joint Committee on Cancer [AJCC] 8th edition) soft tissue sarcoma is required
- Prior partial excision or partial excisional biopsy of the tumor, with imaging evidence of gross residual disease > 1cm in longest dimension (stage II-IIIB)
Participants must have a primary site of disease in the extremity, including the shoulder girdle and hip girdle but excluding the hands and feet
- Participants with primary sites of trunk, head, neck, or intra-abdominal, intrapelvic, or retroperitoneal region are not eligible
- Participants with extension of the primary tumor into adjacent regions (e.g. torso, hands, feet) are eligible
- Participants must have an MRI of the primary site within 90 days prior to randomization. The MRI field of view must contain the entirety of the tumor (may be accomplished with multiple MRI scans). MRI must contain axial acquired T1 weighted with fat suppression, T1 weighted sequence with gadolinium contrast with fat suppression, and T2 weighted fat suppression sequence
Participants must have no evidence of metastatic disease by CT imaging of the chest (or positron emission tomography [PET] CT), within 28 days before randomization
- Given the lack of specificity of chest CT, pulmonary nodule(s) ≤ 5 mm without a histological diagnosis are not exclusionary
- Participants with pulmonary nodule(s) measuring 6-10 mm on chest CT are eligible if the nodules appear stable compared to prior chest imaging from at least 6 months ago, or if an fludeoxyglucose F-18 (18FDG)-PET scan indicates that the nodules are unlikely to be metastatic disease
- Pulmonary nodules > 10 mm should be considered metastatic unless proven otherwise by biopsy/resection or stable appearance for at least 6 months on imaging
- Participants must not have fungating tumor. (i.e., tumor breakthrough of skin)
- Participants must not have myxoid liposarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, gastrointestinal stromal tumor, osteosarcoma, neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm, desmoplastic small round cell tumor, Ewing sarcoma, or sarcoma arising from bone
- Participants must not have known brain metastases. Brain imaging studies are not required for eligibility if the participant has no neurologic signs or symptoms suggestive of brain metastasis. If brain imaging studies are performed, they must be negative for disease
- Participants must have been evaluated by a surgeon, and it must have been determined that they are a good candidate for a limb salvage resection with an expectation of negative margins, within 35 days prior to randomization. Anticipated positive margins on fixed critical structures are allowed
- Participants must not have had prior treatment for the current tumor (systemic therapy, radiation, or complete surgical resection)
- Participants must not have had prior radiation to the anatomical site
- Participants must be ≥ 18 years old at the time of randomization
- Participants must have Zubrod performance status of 0-2
- Participants must have medical history and physical exam within 28 days prior to randomization. History and physical examination must include a description of the location of the tumor, including lateralization and extremity
- Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
- Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
- Participants must not have uncontrolled intercurrent illnesses or any other significant condition(s) that would make this protocol unreasonably hazardous
- Participants with a history human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
- Participants registered by sites located in the United States only must be offered the opportunity to participate in specimen banking
NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
- Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
- For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
有源比较器：Arm 1 (RT-25)
Patients undergo RT-25 with 3D CRT or IMRT QD for up to 5 fractions per week for 25 fractions over a minimum of 32 calendar days and maximum of 49 days in the absence of disease progression or unacceptable toxicity.
Starting 22-56 calendar days after radiation, patients undergo surgical resection.
Additionally, patients undergo MRI, CT, and blood sample collection throughout the study.
|
进行核磁共振
其他名称：
接受CT
其他名称：
进行血液样本采集
其他名称：
接受手术切除
其他名称：
Undergo RT-25 with 3D-CRT
其他名称：
Undergo UHRT-5 with 3D CRT
其他名称：
Undergo RT-25 with IMRT
其他名称：
Undergo UHRT-5 with IMRT
其他名称：
|
|
实验性的：Arm 2 (UHRT-5)
Patients undergo UHRT-5 with 3D CRT or IMRT QD for up to 5 fractions per week for 5 fractions over a minimum of 5 calendar days and maximum of 14 days in the absence of disease progression or unacceptable toxicity.
Starting 22-56 calendar days after radiation, patients undergo surgical resection.
Additionally, patients undergo MRI, CT, and blood sample collection throughout the study.
|
进行核磁共振
其他名称：
接受CT
其他名称：
进行血液样本采集
其他名称：
接受手术切除
其他名称：
Undergo RT-25 with 3D-CRT
其他名称：
Undergo UHRT-5 with 3D CRT
其他名称：
Undergo RT-25 with IMRT
其他名称：
Undergo UHRT-5 with IMRT
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Local tumor recurrence rate
大体时间：At 2 years
|
Cumulative incidence of local tumor recurrence will be estimated non-parametrically with death from any cause analyzed as a competing risk.
2-year estimates of local tumor recurrence and standard errors will be calculated and used to calculate a one-sided 95% confidence internal for the difference in 2-year local tumor recurrence rates.
|
At 2 years
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Incidence of acute wound complications
大体时间：Up to 4 months after surgery
|
Will be estimated in each arm with 95% exact confidence intervals and compared using Fisher's exact test.
|
Up to 4 months after surgery
|
|
Incidence of late-term complications associated with radiation
大体时间：Up to 2 years post-surgery
|
Will be estimated in each arm with 95% exact confidence intervals and compared using Fisher's exact test.
|
Up to 2 years post-surgery
|
|
Changes in physician-assessed functional outcome
大体时间：From pre-randomization up to 24 months post-surgery
|
Will be evaluated using the Musculoskeletal Tumor Society Scoring system.
|
From pre-randomization up to 24 months post-surgery
|
|
Overall survival
大体时间：From randomization up to 10 years
|
Will be estimated in each arm and compared using log-rank tests.
|
From randomization up to 10 years
|
|
Progression-free survival
大体时间：From randomization up to 10 years
|
Will be estimated in each arm and compared using log-rank tests.
|
From randomization up to 10 years
|
|
Distant-metastasis-free survival
大体时间：From randomization up to 10 years
|
Cumulative incidence will be estimated non-parametrically in each arm and compared using Gray's test.
|
From randomization up to 10 years
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Incidence of local tumor recurrence
大体时间：At 2 years
|
Will estimate and compare between arms using a per-protocol analysis and report with 95% confidence intervals.
Will be estimated non-parametrically in each arm based on observed reporting of events without pooling/harmonizing of event times and descriptively reported.
|
At 2 years
|
|
Incidence of delayed wound healing
大体时间：Up to 6 months post-surgery
|
Will estimate and compare between arms the incidence of delayed wound healing and report 95% confidence intervals and compare with Fisher's exact test.
|
Up to 6 months post-surgery
|
|
Type of surgical resection
大体时间：At time of surgery
|
Will report the type of surgical resection by treatment arm, including limb-salvage versus amputation and margin status with exact 95% confidence intervals.
|
At time of surgery
|
|
Use of supportive therapy medications given with radiation therapy
大体时间：Up to 10 years
|
Will describe the use of supportive therapy medications given with radiation therapy separately by treatment arm.
|
Up to 10 years
|
|
Use of adjuvant therapy post-surgery
大体时间：Up to 10 years
|
Will describe the use of adjuvant therapy post-surgery separately by treatment arm.
|
Up to 10 years
|
合作者和调查者
调查人员
- 首席研究员：Jeremy P Harris、SWOG Cancer Research Network
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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