A Phase III Trial of Stereotactic Radiosurgery Compared With Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) Plus Memantine for 5 or More Brain Metastases
概览
- 阶段
- 3 期
- 干预措施
- Stereotactic Radiosurgery (SRS)
- 疾病 / 适应症
- Brain Metastases
- 发起方
- Canadian Cancer Trials Group
- 入组人数
- 206
- 试验地点
- 173
- 主要终点
- Overall Survival
- 状态
- 招募中
- 最后更新
- 18天前
概览
简要总结
Stereotactic radiosurgery (SRS) is a commonly used treatment for brain tumors. It is a one-day (or in some cases two day), out-patient procedure during which a high dose of radiation is delivered to small spots in the brain while excluding the surrounding normal brain.
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) is when radiation therapy is given to the whole brain, while trying to decrease the amount of radiation that is delivered to the area of the hippocampus. The hippocampus is a brain structure that is important for memory. Memantine is a drug that is given to help relieve symptoms that can be caused by WBRT, including problems with memory and other mental symptoms.
Health Canada, the regulatory body that oversees the use of drugs in Canada, has not approved the sale or use of memantine in combination with WBRT to treat this kind of cancer, although they have allowed its use in this study.
详细描述
The purpose of this research study is to compare the effects (good or bad) of receiving stereotactic radiosurgery (SRS) versus receiving hippocampal-avoidant whole brain radiotherapy (HA-WBRT) plus a drug called memantine, on brain metastases. Receiving SRS could control cancer that has spread to the brain. This study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. To decide if it is better, the study doctors will be looking to see if the stereotactic radiosurgery (SRS) helps to either slow the growth of cancer or stop it from coming back, compared to the usual approach. Doctors will also look to see if this new approach increases the life span of patients with this type of cancer, and if it helps with quality of life and cancer related symptoms. The usual approach for patients who are not in a study is treatment with whole brain radiation therapy alone (WBRT).
研究者
入排标准
入选标准
- •Patients must have 5 or more brain metastases as counted on a T1 contrast enhanced MRI obtained ≤ 30 days from randomization (maximum 15 brain metastases).
- •Patients must have a pathological diagnosis (cytological or histological) of a non-hematopoietic malignancy.
- •The largest brain metastasis must measure \<2.5 cm in maximal diameter.
- •Centre must have the ability to treat patients with either a Gamma Knife, Cyberknife, or a linear accelerator-based radiosurgery system.
- •Patient must be \> 18 years of age.
- •Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French either alone or with assistance.
- •ECOG performance status 0, 1, or
- •Creatinine clearance must be ≥ 30 ml/min within 28 days prior to registration.
- •The Neurocognitive Testing examiner must have credentialing confirming completion of the neurocognitive testing training.
- •Facility is credentialed by IROC to perform SRS and HA-WBRT. The treating centre must have completed stereotactic radiosurgery credentialing of the specific system(s) to be used in study patients. The treating centre must have completed IMRT credintialing of this specific IMRT systems to be used in study patients for the purposes of HA-WBRT.
排除标准
- •Pregnant or nursing women.
- •Men or women of childbearing potential who are unwilling to employ adequate contraception.
- •Inability to complete a brain MRI.
- •Known allergy to gadolinium.
- •Prior cranial radiation therapy.
- •Planned cytotoxic chemotherapy within 48 hours prior or after the SRS or HA-WBRT.
- •Primary germ cell tumour, small cell carcinoma, or lymphoma.
- •Widespread definitive leptomeningeal metastasis. This includes cranial nerve palsy, leptomeningeal carcinomatosis, ependymal involvement, cranial nerve involvement on imaging, suspicious linear meningeal enhancement, or cerebrospinal fluid (CSF) positive for tumour cells.
- •A brain metastasis that is located ≤ 5 mm of the optic chiasm or either optic nerve.
- •Surgical resection of a brain metastasis (stereotactic biopsies will be allowed).
研究组 & 干预措施
Stereotactic Radiosurgery (SRS)
SRS 18-20 or 22Gy in single fraction
干预措施: Stereotactic Radiosurgery (SRS)
Hippocampal-avoidant (HA-WBRT) plus Memantine
WBRT 30Gy in 10 fractions + memantine
干预措施: Hippocampal-avoidant (HA-WBRT) Radiotherapy
Hippocampal-avoidant (HA-WBRT) plus Memantine
WBRT 30Gy in 10 fractions + memantine
干预措施: Memantine
结局指标
主要结局
Overall Survival
时间窗: 4.5 years
To compare the overall survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive HA-WBRT + memantine
Neurocognitive progression-free survival
时间窗: 4.5 years
To compare the neurocognitive progression-free survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive HA-WBRT + memantine
次要结局
- Evaluate serial changes in imaging features found in routine MRI images (T2w changes, morphometry) that may predict tumour control and/or neurocognitive outcomes(4.5 years)
- Prospectively validate a predictive nomogram for distant brain failure in patients who receive SRS(4.5 years)
- Quality of life, as assessed by EQ-5D-5L(4.5 years)
- Quality of life assessed by ECOG performance status(4.5 years)
- Collect plasma to evaluate whether detectable somatic mutations in liquid biopsy can enhance prediction of the overall survival and development of new brain metastases.(4.5 years)
- Collect whole-brain dosimetry in SRS patients to be prospectively correlated with cognitive toxicity, intracranial control and radiation necrosis(4.5 years)
- Quality of life, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) with brain cancer module (BN20)(4.5 years)
- Time delay to (re-)initiation of systemic therapy in patients receiving SRS in comparison to HA-WBRT + memantine(4.5 years)
- Compare the estimated cost of brain-related therapies in patients who receive SRS compared to patients who receive HA-WBRT + memantine.(4.5 years)
- Analysis of serum samples for inflammatory biomarker C-reactive protein and brain-derived-neurotrophic factor (BDNF) to elucidate molecular/genomic mechanisms of neurocognitive decline and associated radiographic changes(4.5 years)
- Number of salvage procedures following SRS in comparison to HA-WBRT + memantine(4.5 years)
- Neurocognitive progression-free survival in patients who receive SRS compared to HA-WBRT + memantine(4.5 years)
- Tabulate and descriptively compare the post-treatment adverse events associated with the interventions.(4.5 years)
- Difference in CNS failure patterns (local, distant, or leptomeningeal) in patients who receive SRS compared to patients who receive HA-WBRT + memantine(4.5 years)
- Time to central nervous system (CNS) failure (local, distant, and leptomeningeal) in patients who receive SRS compared to patients who receive HA-WBRT + memantine(4.5 years)