ClinicalTrials.gov
ClinicalTrials.gov Menu

Neuroprotective Effects of Lithium in Patients With Small Cell Lung Cancer Undergoing Radiation Therapy to the Brain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01553916
Recruitment Status : Completed
First Posted : March 14, 2012
Results First Posted : November 8, 2017
Last Update Posted : November 8, 2017
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

March 12, 2012
March 14, 2012
September 7, 2017
November 8, 2017
November 8, 2017
April 26, 2012
September 12, 2016   (Final data collection date for primary outcome measure)
  • Safety of Lithium Carbonate as Measured by Number of Patients in the Safety lead-in Who Experienced a Dose-limiting Toxicity (DLT) [ Time Frame: 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 [ Time Frame: 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
  • Dose-limiting toxicities of lithium (DLTs), (safety lead-in) [ Time Frame: 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.
  • Rate of immediate recall memory deterioration at 3 months, (phase II) [ Time Frame: 3 months ]
    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).
Complete list of historical versions of study NCT01553916 on ClinicalTrials.gov Archive Site
  • Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score [ Time Frame: 6 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
  • Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score [ Time Frame: 12 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
  • Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score [ Time Frame: 3 months ]
    • The HVLT is a word learning test measuring episodic visual memory
    • The delayed 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 20-25 minutes later.
    • The words recalled were recorded and a total recall score tallied (range: 0-36).
    • The higher the score the better the recall
  • Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score [ Time Frame: 6 months ]
    • The HVLT is a word learning test measuring episodic visual memory
    • The delayed 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 20-25 minutes later.
    • The words recalled were recorded and a total recall score tallied (range: 0-36).
    • The higher the score the better the recall
  • Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score [ Time Frame: 12 months ]
    • The HVLT is a word learning test measuring episodic visual memory
    • The delayed 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 20-25 minutes later.
    • The words recalled were recorded and a total recall score tallied (range: 0-36).
    • The higher the score the better the recall
  • Changes in Quality-of-life as Measured by Overall Quality of Life Using the EORTC QLQ30 [ Time Frame: 3 months ]
    • 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)
    • 30 total questions with 28 questions having answers ranging from 1-4 with 1=not at all and 4= very much and 2 questions ranging from 0-7 with 1-very poor and 7=excellent
    • Raw scores will be transformed to a 100-point scale (0=lowest score, 100=highest score)
    • The higher the score the lower the quality of life
  • Changes in Quality-of-life as Measured by Overall Quality of Life Using the Total Score of the EORTC QLQ-BN20 [ Time Frame: 12 months ]

    Assessed by comparing questionnaire test scores to baseline; BN20 (future uncertainty and communications deficit scales)

    • 20 questions with answers ranging from 1-4 with 1=not at all and 4=very much
    • Raw scores will be transformed to a 100-point scale (0=lowest score, 100=highest score)
    • The higher the score the lower quality of life
  • 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 [ Time Frame: 3 months ]
    -Defined as at least 4 of 6 patients successfully completing pre-treatment and 3 month post-treatment testing
  • Change in Hippocampal Morphology Following Lithium + PCI [ Time Frame: 12 months ]
    Hippocampal volume, surface area, and length will be measured using a standardized imaging protocol (magnetization prepared rapid acquisition gradient echo; MPRAGE)
  • Incidence of Brain Metastases [ Time Frame: 12 months ]
    1-year rate of brain metastases together with 95% confidence interval will be calculated based on Kaplan-Meier curve.
  • Incidence of Adverse Events [ Time Frame: 30 days after completion of therapy ]
    Adverse events will be tabulated by type and grade using NCI CTCAE v 4.
  • Overall Survival [ Time Frame: 12 months ]
    Median and 1-year rate of overall survival together with 95% confidence interval will be calculated based on Kaplan-Meier curve.
  • Rate of immediate recall memory deterioration at 6 and 12 months [ Time Frame: 12 months ]
    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 ]
    The percentage of patients with a decrease in HVLT-DR test score compared to baseline.
  • Incidence of Brain Metastases [ Time Frame: 12 months ]
    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 ]
    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 ]
    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 ]
    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: 12 months ]
    Adverse events will be tabulated by type and grade using NCI CTCAE v 4.
Not Provided
Not Provided
 
Neuroprotective Effects of Lithium in Patients With Small Cell Lung Cancer Undergoing Radiation Therapy to the Brain
Phase I/II Trial of Lithium as a Neuroprotective Agent for Patients With Small Cell Lung Cancer (SCLC) Treated With Prophylactic Cranial Irradiation (PCI)
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.
Not Provided
Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Small Cell Lung Carcinoma
  • Drug: Lithium Carbonate
    Other Name: Eskalith, Lithane, Lithium, Lithobid, Lithonate, Lithotabs
  • Radiation: Prophylactic cranial irradiation
    Other Name: PCI
Experimental: 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.

Interventions:
  • Drug: Lithium Carbonate
  • Radiation: Prophylactic cranial irradiation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
19
26
June 5, 2017
September 12, 2016   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01553916
201202073
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Plan to Share IPD: No
Washington University School of Medicine
Washington University School of Medicine
Not Provided
Principal Investigator: Clifford Robinson, M.D. Washington University School of Medicine
Washington University School of Medicine
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP