EXCLAIM: Exploring Combined Local and Systemic Approaches In Brain Metastasis: a Multi-cohort Randomized Phase II Study Evaluating Initial Response to Systemic Therapy and Subsequent Integration of Stereotactic Radiosurgery in Patients With Low-risk Brain Metastases and Central Nervous System-active Systemic Therapy Options
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 316
- 试验地点
- 1
- 主要终点
- Safety and Adverse Events (AEs).
研究概览
简要总结
To learn if consolidative stereotactic radiosurgery (cSRS) can help to control central nervous system (CNS) disease in patients who have brain metastases and have a partial response or stable brain metastases after systemic therapy.
To learn if using SRS to treat all brain metastases that do not respond to systemic therapy versus treating only metastases that are getting worse can help to control CNS disease in patients whose disease gets worse after systemic therapy.
详细描述
Primary Objectives:
To assess whether cSRS improves CNS progression-free survival (CNS-PFS) in patients with BM who have a PR or SD with upfront systemic therapy.
To assess whether SRS to all BM not in CR (cSRS + pdSRS) versus only progressing lesions (pdSRS) improves CNS-PFS in patients with CNS progression on upfront systemic therapy.
Secondary Objectives:
To report the rate and degree of response of BM to systemic therapy by specific regimen and histology.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Age ≥ 18 years.
- •Evaluation by a brain metastasis multidisciplinary team (BM-MDT) consisting of a medical oncologist (can be the patient's primary medical oncologist), a radiation oncologist who regularly performs SRS, and a neurosurgeon. This evaluation can take place in clinic or during a multidisciplinary conference.
- •Life expectancy > 6 months as estimated by BM-MDT.
- •BM-MDT agreement that the planned systemic therapy regimen may provide intracranial benefit (SD, PR, or CR in the CNS).
- •BM-MDT agreement that the patient's BM does not require immediate local therapy (surgery and/or radiation therapy); i.e. it is judged to be safe to omit local therapy as initial BM management.
- •The patient's BM are amenable to SRS as initial local therapy as determined by BM-MDT.
- •Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
- •Histologically confirmed metastatic cancer with at least one measurable metastasis in the brain (≥ 5 mm).
- •At least one measurable intracranial target lesion which was not previously treated with SRS. Regrowth in a cavity of previously excised lesion will not qualify as a measurable lesion. Growth or change in a lesion previously irradiated will not qualify as a measurable lesion.
- •Prior SRS and prior excision of BM is permitted if other measurable non irradiated lesions as described in #9 remain.
- •The resection cavity of excised BM must have received appropriate radiation therapy (pre or post operative SRS, brachytherapy) or have been observed for >6 months after resection without evidence of local cavity recurrence.
- •Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions either without systemic corticosteroids or requiring ≤ 2 mg dexamethasone daily for symptom resolution.
- •ECOG performance status ≤
- •Documented agreement by the patient's primary medical oncologist with the appropriateness of planned SST regimen.
- •This study will allow non-English speaking subjects to be enrolled. Verbal Translation Preparative Sheet (VTPS) will be used if a translated consent form is not available in the subject's language. The consent form will be translated into the language of the subject after 2 or more occurrences. This will apply to any MD Anderson patient.
排除标准
- •History of known leptomeningeal involvement (radiographic or cytological).
- •Small cell lung cancer, lymphoma, or leukemia histology.
- •Non-small cell lung cancer histology with targetable oncogenic driver mutation with planned initiation of highly CNS active targeted therapy (eg osimertinib, brigatinib, alectinib, or lorlatinib).
- •Subjects previously treated with WBRT.
- •Any intact BM size > 3 cm. After surgical excision and appropriate radiation therapy to the cavity, patients may enroll if additional eligible lesions are present.
- •Prior disease progression on one or more of the agents comprising SST.
- •Exposure to one or more agents comprising SST within the last 30 days.
- •Prior unacceptable toxicity during treatment with one or more agents comprising SST.
- •Subjects with a major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled.
- •History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful treatment of superficial bladder cancer, in situ cervical cancer, ductal carcinoma in situ, or other in-situ cancers. Subjects with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
- •Skin Cancer Exclusion: Please note that localized cutaneous basal cell carcinoma and squamous cell carcinoma is not an exclusion criterion regardless of treatment status. Biopsy proven metastatic disease from these histologies is an exclusion criterion if this constitutes a second cancer.
- •Patient weight >450 pounds.
- •Patient had prior SRS to any intracranial lesion <15mm from a metastasis on the screening MRI. Prior MRIs and DICOMs will be used to make this determination.
- •Patient unable to receive a brain MRI (implanted metal devices or foreign bodies) or MRI contrast.
- •Any BM with a significant hemorrhagic component (defined as MRI T1 intrinsic hyperintensity comprising ≥ 25% of maximal lesion diameter).
研究组 & 干预措施
SST treated PD patients to pdSRS / pdSRS+cSRS
At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS.
干预措施: Stereotactic Radiosurgery (Radiation)
cSRS PR or SD
Patients with a CR will be observed with ongoing standard of care MRI. Patients with SD or PR will be randomized to receive cSRS or ongoing observation.
干预措施: Systemic Therapy (Other)
cSRS PR or SD
Patients with a CR will be observed with ongoing standard of care MRI. Patients with SD or PR will be randomized to receive cSRS or ongoing observation.
干预措施: Stereotactic Radiosurgery (Radiation)
a-pdSR CNS PD
At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS.
干预措施: Systemic Therapy (Other)
a-pdSR CNS PD
At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS.
干预措施: Stereotactic Radiosurgery (Radiation)
b-PDC CNS PD
At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS.
干预措施: Systemic Therapy (Other)
b-PDC CNS PD
At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS.
干预措施: Stereotactic Radiosurgery (Radiation)
SST treated SD or PR patients to receive cSRS/ ongoing observation
Patients with a CR will be observed with ongoing standard of care MRI. Patients with SD or PR will be randomized to receive cSRS or ongoing observation.
干预措施: Systemic Therapy (Other)
SST treated SD or PR patients to receive cSRS/ ongoing observation
Patients with a CR will be observed with ongoing standard of care MRI. Patients with SD or PR will be randomized to receive cSRS or ongoing observation.
干预措施: Stereotactic Radiosurgery (Radiation)
SST treated PD patients to pdSRS / pdSRS+cSRS
At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS.
干预措施: Systemic Therapy (Other)
结局指标
主要结局
Safety and Adverse Events (AEs).
时间窗: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
次要结局
未报告次要终点