Neuroprotective Effects of Lithium in Patients With Small Cell Lung Cancer Undergoing Radiation Therapy to the Brain
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
|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)|
- Dose-limiting toxicities of lithium (DLTs), (safety lead-in) [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]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.
- Rate of immediate recall memory deterioration at 3 months, (phase II) [ Time Frame: 3 months ] [ Designated as safety issue: No ]Proportion of patients with deterioration defined as a drop from the HVLT-IR baseline test score that is greater than or equal to the reliable change index (RCI).
- Rate of immediate recall memory deterioration at 6 and 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]Proportion of patients with deterioration, defined as a drop from the HVLT-IR baseline test score that is greater than or equal to the reliable change index (RCI).
- Rate of delayed recall memory deterioration at 3, 6 and 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]The percentage of patients with a decrease in HVLT-DR test score compared to baseline.
- Incidence of brain metastases [ Time Frame: 12 months ] [ Designated as safety issue: No ]1-year rate of brain metastases together with 95% confidence interval will be calculated based on Kaplan-Meier curve.
- Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]Median and 1-year rate of overall survival together with 95% confidence interval will be calculated based on Kaplan-Meier curve.
- Changes in quality-of-life following PCI [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Assessed by comparing questionnaire test scores to baseline; European Organization for Research and Treatment of Cancer (EORTC) QLQ30 (global health/QOL, cognitive functioning, and fatigue scales) and BN20 (future uncertainty and communications deficit scales)
- Change in hippocampal morphology following lithium + PCI [ Time Frame: 12 months ] [ Designated as safety issue: No ]Hippocampal volume, surface area, and length will be measured using a standardized imaging protocol (magnetization prepared rapid acquisition gradient echo; MPRAGE)
- Incidence of adverse events [ Time Frame: 30 days after completion of therapy ] [ Designated as safety issue: Yes ]Adverse events will be tabulated by type and grade using NCI CTCAE v 4.
- Feasibility of performing serial neurocognitive testing and quality of life exams in patients wit [ Time Frame: 12 months ] [ Designated as safety issue: No ]Defined as at least 4 of 6 patients successfully completing pre-treatment and 3 month post-treatment testing
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||April 2017|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
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.
Drug: Lithium Carbonate
Other Name: Eskalith, Lithane, Lithium, Lithobid, Lithonate, Lithotabs
Please refer to this study by its ClinicalTrials.gov identifier: NCT01553916
|Contact: Clifford Robinson, M.D.||email@example.com|
|Contact: Regina Smithfirstname.lastname@example.org|
|United States, Missouri|
|Washinton University School of Medicine||Recruiting|
|St. Louis, Missouri, United States, 63110|
|Sub-Investigator: Dennis Hallahan, M.D.|
|Sub-Investigator: Dinesh Thotala, Ph.D.|
|Sub-Investigator: Jeffrey Bradley, M.D.|
|Sub-Investigator: Todd DeWees, Ph.D.|
|Sub-Investigator: Tammie Benzinger, M.D.|
|Sub-Investigator: Daniel Marcus, Ph.D.|
|Principal Investigator:||Clifford Robinson, M.D.||Washington University School of Medicine|