Trial Outcomes & Findings for Neuroprotective Effects of Lithium in Patients With Small Cell Lung Cancer Undergoing Radiation Therapy to the Brain (NCT NCT01553916)

NCT ID: NCT01553916

Last Updated: 2018-07-05

Results Overview

-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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

19 participants

Primary outcome timeframe

3 weeks

Results posted on

2018-07-05

Participant Flow

Participant milestones

Participant milestones
Measure
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.
Overall Study
STARTED
19
Overall Study
COMPLETED
16
Overall Study
NOT COMPLETED
3

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
Overall Study
Withdrawal by Subject
2
Overall Study
Pre-treatment MRI metastatic disease
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=19 Participants
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.
Age, Continuous
58 years
n=5 Participants
Sex: Female, Male
Female
12 Participants
n=5 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
Region of Enrollment
United States
19 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 3 weeks

Population: -Only patients enrolled in the safety lead-in were evaluable for this outcome measure

-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.

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=6 Participants
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.
Safety of Lithium Carbonate as Measured by Number of Patients in the Safety lead-in Who Experienced a Dose-limiting Toxicity (DLT)
1 Participants

PRIMARY outcome

Timeframe: 3 months

Population: 6 participants were not evaluable for this outcome measure

* 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

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=13 Participants
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.
Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
20.0714 scores on a scale
Standard Deviation 8.29703

SECONDARY outcome

Timeframe: 6 months

Population: 11 participants were not evaluable for this outcome measure

* 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

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=8 Participants
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.
Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
20.2 scores on a scale
Standard Deviation 7.22342

SECONDARY outcome

Timeframe: 12 months

Population: 13 participants were not evaluable for this outcome measure

* 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

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=6 Participants
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.
Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
24.0 scores on a scale
Standard Deviation 4.89898

SECONDARY outcome

Timeframe: 3 months

Population: -8 participants were not evaluable for this outcome measure

* 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

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=11 Participants
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.
Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
8.6923 scores on a scale
Standard Deviation 2.89783

SECONDARY outcome

Timeframe: 6 months

Population: 11 participants were not evaluable for this outcome measure

* 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

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=8 Participants
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.
Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
10.3 scores on a scale
Standard Deviation 1.56702

SECONDARY outcome

Timeframe: 12 months

Population: 13 participants were not evaluable for this outcome measure

* 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

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=6 Participants
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.
Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
10.5 scores on a scale
Standard Deviation 0.83666

SECONDARY outcome

Timeframe: 3 months

Population: 5 participants were not analyzed for this outcome measure

* 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

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=14 Participants
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.
Changes in Quality-of-life as Measured by Overall Quality of Life Using the EORTC QLQ30
45.0820 scores on a scale
Standard Deviation 7.4469

SECONDARY outcome

Timeframe: 12 months

Population: 5 participants were not evaluable for this outcome measure

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

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=14 Participants
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.
Changes in Quality-of-life as Measured by Overall Quality of Life Using the Total Score of the EORTC QLQ-BN20
20.5514 scores on a scale
Standard Deviation 13.8067

SECONDARY outcome

Timeframe: 3 months

Population: (1) participant is not evaluable as the participant did not start treatment due to pre-treatment MRI showing metastatic disease in spine.

-Defined as at least 4 of 6 patients successfully completing pre-treatment and 3 month post-treatment testing

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=18 Participants
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.
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
13 Participants

SECONDARY outcome

Timeframe: Baseline through 12 months

Population: * 10 participants were evaluable for this outcome measure * Originally the outcome measure time frame was baseline through 12 months but there was insufficient data to statistically analyze the change in hippocampal morphology at 12 months due to the number of participants still alive for the 12 month scan.

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=10 Participants
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.
Change in Hippocampal Morphology Following Lithium + PCI as Measured by Total Hippocampal Volume
Baseline
6.13 cc
Interval 5.63 to 7.65
Change in Hippocampal Morphology Following Lithium + PCI as Measured by Total Hippocampal Volume
3 months
6.08 cc
Interval 4.95 to 6.69
Change in Hippocampal Morphology Following Lithium + PCI as Measured by Total Hippocampal Volume
12 months
6.34 cc
Interval 5.2 to 6.8

SECONDARY outcome

Timeframe: 12 months

Population: 7 participants were not evaluable for this outcome measure

1-year rate of brain metastases

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=9 Participants
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.
Number of Participants With Brain Metastases
2 Participants

SECONDARY outcome

Timeframe: Through 12 months

Adverse events will be tabulated by type and grade using NCI CTCAE v 4.

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=19 Participants
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.
Number of Central Nervous System (CNS) Adverse Events
Grade 1
28 CNS adverse events
Number of Central Nervous System (CNS) Adverse Events
Grade 2
6 CNS adverse events
Number of Central Nervous System (CNS) Adverse Events
Grade 3
2 CNS adverse events

SECONDARY outcome

Timeframe: 12 months

Population: 7 participants were not evaluable for this outcome measure

-Overall survival is defined as the time between date of on study and date of death due to any cause

Outcome measures

Outcome measures
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=9 Participants
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.
Rate of Overall Survival
5 Participants

Adverse Events

Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation

Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Arm 1: Lithium Carbonate + Prophylactic Cranial Irradiation
n=19 participants at risk
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.
Blood and lymphatic system disorders
Anemia
31.6%
6/19
Blood and lymphatic system disorders
Red blood cell decrease
5.3%
1/19
Ear and labyrinth disorders
Ear pain
5.3%
1/19
Ear and labyrinth disorders
External ear pain
5.3%
1/19
Ear and labyrinth disorders
Hearing impaired
10.5%
2/19
Ear and labyrinth disorders
Tinnitus
5.3%
1/19
Endocrine disorders
Adrenal insufficiency
5.3%
1/19
Eye disorders
Blurred vision
10.5%
2/19
Eye disorders
Floaters
5.3%
1/19
Gastrointestinal disorders
Constipation
10.5%
2/19
Gastrointestinal disorders
Diarrhea
10.5%
2/19
Gastrointestinal disorders
Dyspepsia
10.5%
2/19
Gastrointestinal disorders
Nausea
47.4%
9/19
Gastrointestinal disorders
Vomiting
36.8%
7/19
General disorders
Chills
10.5%
2/19
General disorders
Edema face
5.3%
1/19
General disorders
Fatigue
57.9%
11/19
General disorders
Fever
10.5%
2/19
General disorders
Flu like symptoms
5.3%
1/19
General disorders
Gait disturbance
10.5%
2/19
General disorders
Malaise
5.3%
1/19
General disorders
Non-cardiac chest pain
5.3%
1/19
Infections and infestations
Bronchial infection
10.5%
2/19
Infections and infestations
Lung infection
10.5%
2/19
Infections and infestations
Sinusitis
5.3%
1/19
Injury, poisoning and procedural complications
Dermatitis radiation
15.8%
3/19
Injury, poisoning and procedural complications
Fall
5.3%
1/19
Injury, poisoning and procedural complications
Spinal fracture
5.3%
1/19
Investigations
Alanine aminotransferase increased
15.8%
3/19
Investigations
Alkaline phosphatase increased
5.3%
1/19
Investigations
Aspartate aminotransferase increased
15.8%
3/19
Investigations
Creatinine increased
10.5%
2/19
Investigations
INR increased
5.3%
1/19
Investigations
Lymphocyte count decreased
47.4%
9/19
Investigations
Neutrophil count decreased
15.8%
3/19
Investigations
Platelet count decreased
10.5%
2/19
Investigations
Weight gain
5.3%
1/19
Investigations
Weight loss
15.8%
3/19
Investigations
White blood cell decreased
15.8%
3/19
Metabolism and nutrition disorders
Anorexia
36.8%
7/19
Metabolism and nutrition disorders
Hypercalcemia
5.3%
1/19
Metabolism and nutrition disorders
Hyperkalemia
10.5%
2/19
Metabolism and nutrition disorders
Hypernatremia
5.3%
1/19
Metabolism and nutrition disorders
Hypoalbuminemia
10.5%
2/19
Metabolism and nutrition disorders
Hypocalcemia
10.5%
2/19
Metabolism and nutrition disorders
Hypokalemia
10.5%
2/19
Metabolism and nutrition disorders
Hyponatremia
15.8%
3/19
Musculoskeletal and connective tissue disorders
Arthralgia
21.1%
4/19
Musculoskeletal and connective tissue disorders
Back pain
15.8%
3/19
Musculoskeletal and connective tissue disorders
Chest wall pain
5.3%
1/19
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
10.5%
2/19
Musculoskeletal and connective tissue disorders
Myalgia
10.5%
2/19
Musculoskeletal and connective tissue disorders
Neck pain
5.3%
1/19
Musculoskeletal and connective tissue disorders
Other - sacroiliac pain
5.3%
1/19
Musculoskeletal and connective tissue disorders
Other - right leg pain
5.3%
1/19
Musculoskeletal and connective tissue disorders
Pain in extremity
5.3%
1/19
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Other - disease progression
5.3%
1/19
Nervous system disorders
Concentration impairment
5.3%
1/19
Nervous system disorders
Dizziness
47.4%
9/19
Nervous system disorders
Dysgeusia
26.3%
5/19
Nervous system disorders
Headache
52.6%
10/19
Nervous system disorders
Memory impairment
10.5%
2/19
Nervous system disorders
Nystagmus
5.3%
1/19
Nervous system disorders
Other - myoclonic jerk
5.3%
1/19
Nervous system disorders
Paresthesia
5.3%
1/19
Nervous system disorders
Peripheral motor neuropathy
5.3%
1/19
Nervous system disorders
Peripheral sensory neuropathy
10.5%
2/19
Nervous system disorders
Somnolence
5.3%
1/19
Nervous system disorders
Tremor
10.5%
2/19
Psychiatric disorders
Anxiety
10.5%
2/19
Psychiatric disorders
Confusion
26.3%
5/19
Psychiatric disorders
Depression
10.5%
2/19
Renal and urinary disorders
Acute kidney injury
5.3%
1/19
Respiratory, thoracic and mediastinal disorders
Atelectasis
5.3%
1/19
Respiratory, thoracic and mediastinal disorders
Cough
10.5%
2/19
Respiratory, thoracic and mediastinal disorders
Dyspnea
26.3%
5/19
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
5.3%
1/19
Respiratory, thoracic and mediastinal disorders
Pneumonitis
5.3%
1/19
Respiratory, thoracic and mediastinal disorders
Sore throat
5.3%
1/19
Skin and subcutaneous tissue disorders
Alopecia
10.5%
2/19
Skin and subcutaneous tissue disorders
Rash acneiform
5.3%
1/19
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
5.3%
1/19
Vascular disorders
Thromboembolic event
5.3%
1/19

Additional Information

Clifford Robinson, M.D.

Washington University School of Medicine

Phone: 314-362-4653

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place