Back to resultsNeuroprotective Effects of Lithium in Patients With Small Cell Lung Cancer Undergoing Radiation Therapy to the Brain
Primary Purpose
Small Cell Lung Carcinoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lithium Carbonate
Prophylactic cranial irradiation
Sponsored by
About this trial
This is an interventional supportive care trial for Small Cell Lung Carcinoma
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
Sites / Locations
- Washinton University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm 1: Lithium carbonate + prophylactic cranial irradiation
Arm Description
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.
Outcomes
Primary Outcome Measures
Safety of Lithium Carbonate as Measured by Number of Patients in the Safety lead-in Who Experienced a Dose-limiting Toxicity (DLT)
-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
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
Secondary Outcome Measures
Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
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
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
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
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
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
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
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
-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 as Measured by Total Hippocampal Volume
Number of Participants With Brain Metastases
1-year rate of brain metastases
Number of Central Nervous System (CNS) Adverse Events
Adverse events will be tabulated by type and grade using NCI CTCAE v 4.
Rate of Overall Survival
-Overall survival is defined as the time between date of on study and date of death due to any cause
Full Information
NCT ID
NCT01553916
First Posted
March 12, 2012
Last Updated
July 3, 2018
Sponsor
Washington University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT01553916
Brief Title
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
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
April 26, 2012 (Actual)
Primary Completion Date
September 12, 2016 (Actual)
Study Completion Date
June 5, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Carcinoma
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: Lithium carbonate + prophylactic cranial irradiation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lithium Carbonate
Other Intervention Name(s)
Eskalith, Lithane, Lithium, Lithobid, Lithonate, Lithotabs
Intervention Type
Radiation
Intervention Name(s)
Prophylactic cranial irradiation
Other Intervention Name(s)
PCI
Primary Outcome Measure Information:
Title
Safety of Lithium Carbonate as Measured by Number of Patients in the Safety lead-in Who Experienced a Dose-limiting Toxicity (DLT)
Description
-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.
Time Frame
3 weeks
Title
Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
Description
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
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
Description
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
Time Frame
6 months
Title
Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
Description
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
Time Frame
12 months
Title
Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
Description
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
Time Frame
3 months
Title
Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
Description
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
Time Frame
6 months
Title
Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
Description
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
Time Frame
12 months
Title
Changes in Quality-of-life as Measured by Overall Quality of Life Using the EORTC QLQ30
Description
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
Time Frame
3 months
Title
Changes in Quality-of-life as Measured by Overall Quality of Life Using the Total Score of the EORTC QLQ-BN20
Description
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
Time Frame
12 months
Title
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
Description
-Defined as at least 4 of 6 patients successfully completing pre-treatment and 3 month post-treatment testing
Time Frame
3 months
Title
Change in Hippocampal Morphology Following Lithium + PCI as Measured by Total Hippocampal Volume
Time Frame
Baseline through 12 months
Title
Number of Participants With Brain Metastases
Description
1-year rate of brain metastases
Time Frame
12 months
Title
Number of Central Nervous System (CNS) Adverse Events
Description
Adverse events will be tabulated by type and grade using NCI CTCAE v 4.
Time Frame
Through 12 months
Title
Rate of Overall Survival
Description
-Overall survival is defined as the time between date of on study and date of death due to any cause
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clifford Robinson, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washinton University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Learn more about this trial
Neuroprotective Effects of Lithium in Patients With Small Cell Lung Cancer Undergoing Radiation Therapy to the Brain
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