Early Prophylactic Cranial Irradiation With Hippocampal Avoidance in Patients With Limited Disease Small-cell Lung Cancer. A Multicenter Phase II Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 16
- 主要终点
- Neurocognitive functioning (NCF)
研究概览
简要总结
The main objective of this trial is to assess NCF after early HA-PCI concomitant to the second cycle of CHT and to tRT for patients with LD SCLC.
详细描述
About 15% of all lung cancers are small cell lung cancer (SCLC). SCLC is a high-grade, neuroendocrine carcinoma of the lung. Limited disease (LD) SCLC is confined to the hemithorax of origin, the mediastinum, or the supraclavicular nodes, which can be encompassed within a tolerable radiation therapy port. About 30% of all SCLC are LD at diagnosis. The median overall survival (OS) in LD SCLC is approximately 20 months, with an expected 5-year survival of less than 15%.
SCLC is characterized by rapid growth and early dissemination. The standard treatment of LD SCLC involves multimodality therapy with concurrent thoracic radiotherapy (tRT) and chemotherapy (CHT) with cisplatin and etoposide.
Recurrence in the brain is usually the primary site of treatment failure in SCLC and is associated with significant morbidity; and consequently often the cause of death. Occult early dissemination of SCLC has frequently occurred prior to the time of diagnosis. In patients with brain metastasis two randomized trials showed an overall 5-year rate of brain metastasis of 59% without prophylactic cranial irradiation (PCI) compared to 43% with PCI. However the rate of brain metastasis with PCI is still very high.
About 50% of patients with SCLC will develop brain metastases some time during the course of their disease. Therefore PCI is recommended in case of good response to CHT and tRT. PCI has shown to improve overall survival in patients with LD who have achieved a complete or partial remission after initial chemoradiotherapy. CHT might achieve insufficient drug levels in the brain. Therefore, an up-front PCI could treat occult brain metastases at a preclinical state and may increase the permeability of the blood-brain barrier for CHT products.
When evaluating PCI it is important to weigh the reduced incidence of brain metastases against the potential risk of deficits resulting from the treatment itself, including deteriorations in neurocognitive functions (NCF) or quality of life (QoL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed cytologically or histologically confirmed diagnosis of SCLC within 6 weeks before registration.
- •Proven LD SCLC (CT thorax, abdomen, and bone scan (or PET/CT only) and brain MRI within 6 weeks before registration) according to the TNM classification version 7 that can be encompassed within a radical radiation port
- •Only patients assessed by an interdisciplinary tumor board should be declared eligible taking into account eligibility for curative tRT and CHT according to NCCN Guidelines version 2.2014
- •Karnofsky Index ≥ 60%
- •Age at registration 18 to 75 years
- •Normal bone marrow function: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L
- •Calculated creatinine clearance ≥ 60 mL/min is required if chemotherapy with cisplatin is scheduled. If cisplatin has to be replaced by carboplatin a creatinine clearance ≥ 50 mL/min is required
- •Normal liver function: bilirubin ≤ 1 x ULN, AST and ALT ≤1.5 x ULN
- •Fluency in either German, French or Italian
- •Women are not breastfeeding. Women with child-bearing potential are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 6 months thereafter. A negative pregnancy test before inclusion (within 7 days) into the trial is required for all women with child-bearing potential. Men agree not to father a child during participation in the trial and during 6 months thereafter.
- •Baseline QoL questionnaires FACT-Br and GHQ-12 have been completed within 14 days before registration
- •Baseline NCF assessments have been completed within 14 days before registration:
- •Patient must give written informed consent before registration
排除标准
- •Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
- •History of CNS metastases
- •Prior brain RT
- •History of RT to the thorax
- •Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling out QoL forms, participating in assessing NCF testing or interfering with compliance for oral drug intake.
- •Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to trial entry.
- •Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes).
- •Any concomitant drugs contraindicated for use with the treatment drugs according to the approved product information.
- •History of cerebrovascular disease or epilepsy requiring continuous treatment
- •Symptomatic cardiac disease or a history of myocardial infarction within the previous 3 months
- •Any psychological, familial or sociological/geographical conditions potentially hampering compliance with the study protocol and follow-up schedule
- •Legal incapacity or limited legal capacity
结局指标
主要结局
Neurocognitive functioning (NCF)
时间窗: at 6 months
NCF at 6 months after end of HA-PCI treatment measured by Hopkins Verbal Learning Test Revised (HVLT-R), Controlled Oral Word Association (COWAT) and Trail Making Test Part A and B (TMT A/B). A neurocognitive decline is defined as a decrease of one standard error of measurement (SEM) in any of the four NCF tests.
次要结局
- Adverse events according to NCI CTCAE version 4.0(Until 1 year after the end of HA-PCI treatment.)
- Neurotoxicity(Until 1 year after HA-PCI treatment.)
- Brain metastasis free survival (BMFS)(At 6 months and 12 months.)
- Individual tests for each cognitive domain (memory, verbal fluency, visual motor speed, executive function).(At 6 weeks, 6 and 12 months after the end of HA-PCI treatment.)
- Overall survival (OS)(From time of registration (expected average of 20 months))
- Quality of Life (QoL) measured by functional assessment of cancer therapy-brain (FACT-Br) and general health questionnaire (GHQ-12)(At 6 weeks, 6 and 12 months after the end of HA-PCI treatment.)