Clinical trial NCT01553916: Neuroprotective Effects of Lithium in Patients With Small Cell Lung Cancer Undergoing Radiation Therapy to the Brain
Official title: Phase I/II Trial of Lithium as a Neuroprotective Agent for Patients With Small Cell Lung Cancer (SCLC) Treated With Prophylactic Cranial Irradiation (PCI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Small Cell Lung Carcinoma
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2012-03-14
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Safety of Lithium Carbonate as Measured by Number of Patients in the Safety lead-in Who Experienced a Dose-limiting Toxicity (DLT)
timeFrame: 3 weeks
measure: Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
timeFrame: 3 months
Secondary outcomes:
measure: Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
timeFrame: 6 months
measure: Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
timeFrame: 12 months
measure: Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
timeFrame: 3 months
measure: Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
timeFrame: 6 months
measure: Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
timeFrame: 12 months
measure: Changes in Quality-of-life as Measured by Overall Quality of Life Using the EORTC QLQ30
timeFrame: 3 months
measure: Changes in Quality-of-life as Measured by Overall Quality of Life Using the Total Score of the EORTC QLQ-BN20
timeFrame: 12 months
measure: 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
timeFrame: 3 months
measure: Change in Hippocampal Morphology Following Lithium + PCI as Measured by Total Hippocampal Volume
timeFrame: Baseline through 12 months
measure: Number of Participants With Brain Metastases
timeFrame: 12 months
measure: Number of Central Nervous System (CNS) Adverse Events
timeFrame: Through 12 months
measure: Rate of Overall Survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washinton University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Clifford Robinson, M.D.
role: PRINCIPAL_INVESTIGATOR
References: