临床试验/NCT02635009

NCT02635009已完成2 期

Randomized Phase II/III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small Cell Lung Cancer

NRG Oncology281 个研究点分布在 1 个国家目标入组 418 人开始时间: 2015年12月22日最近更新: 2026年7月10日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: NRG Oncology
入组人数: 418
试验地点: 281
主要终点: Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This randomized phase II/III trial studies how well whole-brain radiation therapy works and compares it with or without hippocampal avoidance in treating patients with small cell lung cancer that is found in one lung, the tissues between the lungs, and nearby lymph nodes only (limited stage) or has spread outside of the lung in which it began or to other parts of the body (extensive stage). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The hippocampus is part of the brain that is important for memory. Avoiding the hippocampus during whole-brain radiation could decrease the chance of side effects on memory and thinking. It is not yet known whether giving whole-brain radiation therapy is more effective with or without hippocampal avoidance in treating patients with small cell lung cancer.

详细描述

PRIMARY OBJECTIVES:

I. Determine whether the 12-month intracranial relapse rate following hippocampal avoidance (HA)-prophylactic cranial irradiation (PCI) is non-inferior compared to the rate following PCI for patients with small cell lung cancer (SCLC). (Randomized Phase II Component [Non-Inferiority]) II. Determine whether HA-PCI reduces the likelihood of 6-month deterioration from baseline in Hopkins Verbal Learning Test (HVLT)-Revised (R) delayed recall compared to PCI for patients with SCLC. (Phase III Component [Efficacy])

SECONDARY OBJECTIVES:

I. Compare time to cognitive failure, as measured by a battery of tests (HVLT-R, Controlled Oral Word Association (COWA) test, and Trail Making Test (TMT) parts A and B), after PCI versus HA-PCI in SCLC.

II. Compare time to cognitive failure as separately measured by each test (HVLT-R for Total Recall and Delayed Recognition, COWA test, and TMT parts A and B), after PCI versus HA-PCI for SCLC.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Supportive Care
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

•[prior to Step 1 registration]:
•Histologic proof or unequivocal cytologic proof (fine needle aspiration, biopsy or two positive sputa) of SCLC within 250 days prior to Step 1 registration
•High-grade neuroendocrine carcinoma or combined SCLC and NSCLC is permitted.
•Patients must have received chemotherapy and be registered to Step 1 registration no earlier than 7 days and no later than 56 days after completing chemotherapy. Note:
•Post-chemotherapy restaging imaging must be completed no more than 56 days prior to Step 1 registration.
•For patients with extensive-stage small cell lung cancer who are being considered for consolidative thoracic radiotherapy after chemotherapy, concomitant administration of consolidative thoracic radiotherapy and protocol-specified prophylactic cranial irradiation with or without hippocampal avoidance is permitted.
•Patients must have a gadolinium contrast-enhanced three-dimensional (3D), spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan. To yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE or TFE axial MRI scan must use the smallest possible axial slice thickness not exceeding 1.5 mm.
•This MRI must be obtained within 56 days prior to Step 1 registration. Note: The MRI study is mandatory irrespective of randomization to the experimental or control arm of this study.
•Prior to chemotherapy +/- thoracic radiotherapy, patients must be defined as limited-stage or extensive-stage SCLC after clinical staging evaluation involving the following:
•History/physical examination;
•CT of the chest and abdomen with contrast (does not have to be done if the patient has had a positron emission tomography (PET) / CT scan prior to initiating chemotherapy or thoracic radiotherapy);
•MRI of the brain with contrast or diagnostic head CT with contrast;
•For patients without evidence of extensive-stage SCLC on chest and abdomen CT and brain MRI or head CT, a PET/CT or bone scan is required to confirm limited-stage SCLC.
•After chemotherapy, patients must be restaged prior to Step 1 registration using the same diagnostic work-up as required pre-chemotherapy. Repeat PET/CT or bone scan is not required. Patients must have:
•History/physical examination within 30 days of Step 1 registration;
•No CNS metastases (Repeat MRI required) within 56 days prior to Step 1 registration;
•No progression in any site;
•Radiographic partial or complete response to chemotherapy in at least one disease site within 56 days prior to Step 1 registration.
•If PET/CT was obtained prior to chemotherapy, either a repeat PET/CT or CT of the chest and abdomen with contrast can be obtained for response assessment.
•Patients who underwent resection for limited-stage SCLC prior to chemotherapy and have no radiographically evident disease for response assessment remain eligible if post-chemotherapy imaging demonstrates no progression.
•Zubrod performance status 0-2 within 30 days prior to Step 1 registration.
•Women of childbearing potential must have a negative qualitative serum pregnancy test =< 14 days prior to Step 1 registration.
•Patients who are primary English or French speakers are eligible
•Patients must sign a study-specific informed consent prior to study entry
•Inclusion Criteria [prior to Step 2 registration]:
•The following baseline neurocognitive assessments must be completed and uploaded within 10 calendar days after or at the time of Step 1 registration: HVLT-R (recall, delayed recall, and recognition), TMT (Parts A and B), and COWA. The neurocognitive assessments will be uploaded into the NRG Oncology Rave System for evaluation by Neurocognitive Co-Chair. Once the upload is complete, within 3 business days, a notification email will be sent to the site to proceed to Step 2 registration. At minimum, the HVLT-R delayed recall must be able to be scored (i.e. completed without error) in order to be eligible.
•Patients must have a baseline raw score greater than 2 on the HVLT-R delayed recall as determined by central assessment by the Neurocognitive Co-Chair.

排除标准

•Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
•Radiographic evidence of central nervous system (CNS) metastases
•Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt
•Planned concurrent chemotherapy during PCI
•Concurrent atezolizumab permitted
•Concomitant invasive malignancy or invasive malignancy within the past five years other than non-melanomatous skin cancer; history of in situ carcinoma (e.g. ductal carcinoma in situ of breast, in situ carcinoma of the cervix, vulva or larynx) is permitted
•Contraindication to MR imaging, such as implanted metal devices or foreign bodies or severe claustrophobia
•Severe, active comorbidity, defined as follows:
•Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
•Transmural myocardial infarction within the last 6 months
•Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
•Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
•Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
•Uncontrolled, clinically significant cardiac arrhythmias
•HIV positive with CD4 count < 200 cells/microliter;
•Note: Patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to Step 1 registration.
•Note: HIV testing is not required for eligibility for this protocol.
•Pregnant or lactating women or women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic.

研究组 & 干预措施

PCI using 3DCRT

Active Comparator

Prophylactic cranial irradiation (PCI) using three-dimensional conformal radiation therapy (3DCRT) for 2 weeks, 5 fractions/week.

干预措施: Three-Dimensional Conformal Radiation Therapy (Radiation)

PCI with HA using IMRT

Experimental

PCI with hippocampal avoidance (HA) using intensity-modulated radiation therapy (IMRT) for 2 weeks, 5 fractions/week.

干预措施: Intensity-Modulated Radiation Therapy (Radiation)

结局指标

主要结局

Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III)

时间窗: Baseline and six months

The HVLT-R delayed recall test assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials to recall after a 20-minute delay. The score is the sum of the number of words correctly recalled and ranges from 0 to 36, with a higher score indicating better functioning. Deterioration is defined a decrease from baseline of at least 3 points.

Number of Participants With Intracranial Relapse at 12 Months (Phase II)

时间窗: From baseline to 12 months

Intracranial relapse, defined as the development of a new brain metastasis as documented on brain MRI with contrast or head CT with contrast.

次要结局

Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)(Baseline, 18, 24 months.)
Number of Participants With Deterioration in TMT Part B Score (Phase III)(Baseline, 18, 24 months.)
Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)(Baseline, 18, 24 months.)
Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III)(Baseline,18, 24 months.)
Number of Participants by Highest Grade Adverse Event Reported (Phase III)(From start of treatment to last known follow-up . Maximum follow-up time was 7.2 years.)
Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)(Baseline,18, 24 months.)
Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)(Baseline,18, 24 months.)
Incremental Cost-per Quality-adjusted Life Year (QALY) (Cost-effectiveness as Measured by the EQ-5D (Phase III)(Baseline to two years)
Percentage of Participants With Neurocognitive Failure (Phase III)(Randomization to date of failure, death, or last known follow-up whichever occurred first. Maximum follow-up at time of analysis was 7.2 years.)
Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)(Baseline, 18, 24 months.)
Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)(Baseline,18, 24 months.)
Number of Participants With Deterioration in EORTC QLQ-BN20 Motor Dysfunction Score (Phase III)(Baseline,18, 24 months.)
Intracranial Relapse Rate (Phase III)(From date of randomization to date of intracranial relapse, death, or last known follow-up, whichever occurred first. Maximum follow-up at time of analysis was 7.2 years.)
White Matter Injury and Hippocampal Volume on Neurocognitive Function (Phase III)(Baseline to 6 months)
Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)(Baseline,18, 24 months.)
Number of Participants With Deterioration in EORTC QLQ-C30 Global Health Status (Phase III)(Baseline,18, 24 months.)
Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)(Baseline,18, 24 months.)
Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III)(Baseline, 3, 6, 12 months.)
Overall Survival (Phase III)(From the date of randomization to the date of death or last follow-up. Maximum follow-up time at time of analysis was 7.2 years.)
Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)(Baseline,18, 24 months.)
Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)(Baseline,18, 24 months.)
Correlation of Quality of Life and Neurocognitive Function (NCF) Measures at 6 Months(6 months)
Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)(Baseline, 3, 12 months.)
Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in TMT Part B Score (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)(Baseline, 3, 6, 12 months.)
Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)(Baseline, 3, 6, 12 months.)

研究者

发起方

NRG Oncology

申办方类型

Other

责任方

Sponsor

研究点 (281)

Loading locations...

相似试验

暂停

2 期

NCT01810913National Cancer Institute (NCI)613

招募中

3 期

Efficacy and Safety of Prophylactic Cranial Irradiation Versus MRI Surveillance in Patients With Limited-stage Small Cell Lung Cancer Who Achieved Remission After First-line ChemoradiotherapyLimited Stage Small Cell Lung Cancer

NCT04829708Shandong Cancer Hospital and Institute534

已完成

2 期

Radiation Therapy, Bevacizumab, Paclitaxel, and Carboplatin in Treating Patients With Unresectable Stage IIIB or Stage IV Non-Small Cell Lung Cancer at High Risk for Hemoptysis Caused by BevacizumabAdenosquamous Cell Lung CancerDrug/Agent Toxicity by Tissue/OrganHemoptysisSquamous Cell Lung CancerStage IIIB Non-small Cell Lung CancerStage IV Non-small Cell Lung Cancer

NCT00387374National Cancer Institute (NCI)72

进行中（未招募）

2 期

Proton Craniospinal Radiation Therapy vs. Partial Photon Radiation Therapy for Leptomeningeal Metastasis From Solid TumorsLeptomeningeal Metastases

NCT04343573Memorial Sloan Kettering Cancer Center102

进行中（未招募）

3 期

A Phase 3 Study of VSA001 in Chinese Adults With Familial Chylomicronemia SyndromeFamilial Chylomicronemia Syndrome

NCT05902598Visirna Therapeutics HK Limited37