Phase I/II Trial of Lithium as a Neuroprotective Agent for Patients With Small Cell Lung Cancer (SCLC) Treated With Prophylactic Cranial Irradiation (PCI)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Safety of Lithium Carbonate as Measured by Number of Patients in the Safety lead-in Who Experienced a Dose-limiting Toxicity (DLT)
研究概览
简要总结
This phase I/II trial studies the effects and safety of giving lithium carbonate (lithium) to patients with small cell lung cancer (SCLC) undergoing radiation therapy to the brain (PCI; prophylactic cranial irradiation). PCI is used to prevent cancer metastases from returning in the brain. This treatment can cause short-term memory problems by damaging the hippocampus. Lithium may help prevent or lessen memory problems caused by PCI by protecting the hippocampus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patient must have histologically or cytologically confirmed small cell lung cancer. Patients with either limited or extensive stage disease are eligible.
- •Patient must have completed 4-6 cycles of platinum-based chemotherapy (+/- thoracic radiotherapy).
- •Patient must have no evidence of progressive disease on restaging imaging within 3 months of enrollment
- •For patients taking medications known to have a significant interaction with lithium carbonate, these medications should be discontinued at least 1 week prior to and during lithium treatment
- •Patient must be > or = 18 years old.
- •Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- •Leukocytes >= 3,000/mcL
- •Absolute neutrophil count >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 3.0 x IULN
- •Creatinine within normal institutional limits OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Patient must have an electrocardiogram without evidence of arrhythmia, QT prolongation (QTc > 450 ms in males and > 470 ms in females), or other severe dysfunction within 2 weeks of initiation of lithium
- •Women of childbearing potential (women with regular menses, women with amenorrhea, women with irregular cycles, women using a contraceptive method that precludes withdrawal bleeding, and women who have had a tubal ligation) are required to have a negative urine pregnancy test within 14 days prior to the first dose of lithium.
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
- •Patient (or legally authorized representative if applicable) must be able to understand and willing to sign an Internal Review Board (IRB) approved written informed consent document
排除标准
- •Patient must not have history of prior cranial radiotherapy
- •Patient must not have brain metastases present prior to initiation of initial therapy or PCI
- •Patient must not have evidence of progressive disease
- •Patient must not have received chemotherapy within 3 weeks of initiation of PCI
- •Patient must not have a history of other malignancy =< 2 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix
- •Patient must not be actively receiving any other investigational agents
- •Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to lithium carbonate
- •Patient must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Patient must not have any uncontrolled thyroid disease
- •Patient must not have a seizure disorder
- •Patient must not be pregnant and/or breastfeeding
研究组 & 干预措施
Arm 1: Lithium carbonate + prophylactic cranial irradiation
Lithium carbonate 300 mg PO BID for 7 days prior to the start of prophylactic cranial irradiation (PCI) and will be continued during PCI.
PCI will be given at 2.5 Gy per fraction, 5 days per week, for 2 weeks to a total dose of 25 Gy, starting on Day 8 after 7 days of lithium.
干预措施: Lithium Carbonate (Drug)
Arm 1: Lithium carbonate + prophylactic cranial irradiation
Lithium carbonate 300 mg PO BID for 7 days prior to the start of prophylactic cranial irradiation (PCI) and will be continued during PCI.
PCI will be given at 2.5 Gy per fraction, 5 days per week, for 2 weeks to a total dose of 25 Gy, starting on Day 8 after 7 days of lithium.
干预措施: Prophylactic cranial irradiation (Radiation)
结局指标
主要结局
Safety of Lithium Carbonate as Measured by Number of Patients in the Safety lead-in Who Experienced a Dose-limiting Toxicity (DLT)
时间窗: 3 weeks
-Graded and described using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4. Safety will be defined as \< 2 patients experiencing DLTs of the first 6 treated.
Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
时间窗: 3 months
* The HVLT is a word learning test measuring episodic visual memory * The immediate recall memory deterioration test portion consists of 36 words split into 3 sections (animals, gemstones, places of shelter, types of birds, tools, items of clothing, kitchen utensils,weapons, and alcoholic beverages) * The words were read aloud and the participants was asked to freely recall them immediately. The list was read a second time followed by a second free recall trial. This was followed by a third reading and third free recall. * The words recalled for each trial were recorded and a total recall score tallied (range: 0-36). * The higher the score the better the recall
次要结局
- Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score(12 months)
- Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score(12 months)
- Changes in Quality-of-life as Measured by Overall Quality of Life Using the EORTC QLQ30(3 months)
- Changes in Quality-of-life as Measured by Overall Quality of Life Using the Total Score of the EORTC QLQ-BN20(12 months)
- Feasibility of Performing Serial Neurocognitive Testing and Quality of Life Exams as Measured by Number of Patients Who Complete the Neurocognitive Testing and Quality of Life Exams(3 months)
- Change in Hippocampal Morphology Following Lithium + PCI as Measured by Total Hippocampal Volume(Baseline through 12 months)
- Number of Participants With Brain Metastases(12 months)
- Number of Central Nervous System (CNS) Adverse Events(Through 12 months)
- Rate of Overall Survival(12 months)