Small Cell Lung CarcinomaPhase 1/2NCT01553916
Neuroprotective Effects of Lithium in Patients With Small Cell Lung Cancer Undergoing Radiation Therapy to the Brain
A Phase 1/2 study testing Lithium Carbonate and Prophylactic cranial irradiation in people with Small Cell Lung Carcinoma, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Carcinoma
- What is being tested?
- Lithium Carbonate and Prophylactic cranial irradiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Apr 2012to 5 Jun 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washinton University School of Medicine
St Louis, Missouri, 63110
About this study
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)
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.
- Conditions
- Small Cell Lung Carcinoma
- Being tested
- Lithium Carbonate, Prophylactic cranial irradiation
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lithium CarbonateDrug
Also called Eskalith, Lithane, Lithium, Lithobid, Lithonate, Lithotabs
Prophylactic cranial irradiationRadiation
Also called PCI
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Lithium carbonate + prophylactic cranial irradiation | Experimental | 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. Receives: Drug: Lithium Carbonate; Radiation: Prophylactic cranial irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 weeks
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
Measured: 3 months
Secondary outcomes (12)
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
Measured: 6 months
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
Measured: 12 months
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
Measured: 3 months
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
Measured: 6 months
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
Measured: 12 months
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
Measured: 3 months
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
Measured: 12 months
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
Measured: 3 months
Change in Hippocampal Morphology Following Lithium + PCI as Measured by Total Hippocampal Volume
Measured: Baseline through 12 months
Number of Participants With Brain Metastases
1-year rate of brain metastases
Measured: 12 months
Number of Central Nervous System (CNS) Adverse Events
Adverse events will be tabulated by type and grade using NCI CTCAE v 4.
Measured: Through 12 months
Rate of Overall Survival
-Overall survival is defined as the time between date of on study and date of death due to any cause
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2012 (estimated)
- Study start26 Apr 2012
- Primary completion12 Sep 2016
- Study completion5 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Clifford Robinson, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01553916
- Sponsor's protocol ID
- 201202073
- Status last verified
- Jul 2018
- First submitted
- 12 Mar 2012
- Last updated
- 5 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01553916
- Acronym / sponsor ID
- 201202073
- Conditions
- Small Cell Lung Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 26 Apr 2012 (actual)
- Primary completion
- 12 Sep 2016 (actual)
- Study completion
- 5 Jun 2017 (actual)
- First posted
- 14 Mar 2012 (estimated)
- Results
- Posted 8 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Lithium carbonate + prophylactic cranial irradiation | Experimental | Drug: Lithium Carbonate, Radiation: Prophylactic cranial irradiationLithium 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithium CarbonateAlso: Eskalith, Lithane, Lithium, Lithobid, Lithonate, Lithotabs | Drug | Arm 1: Lithium carbonate + prophylactic cranial irradiation |
| Prophylactic cranial irradiationAlso: PCI | Radiation | Arm 1: Lithium carbonate + prophylactic cranial irradiation |
Primary outcome
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
12 secondary outcomes
Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
Time frame: 6 months
Immediate Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Immediate Recall (HVLT-IR) Total Score
Time frame: 12 months
Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
Time frame: 3 months
Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
Time frame: 6 months
Delayed Recall Memory Deterioration as Measured by the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR) Total Score
Time frame: 12 months
Changes in Quality-of-life as Measured by Overall Quality of Life Using the EORTC QLQ30
Time frame: 3 months
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
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
Change in Hippocampal Morphology Following Lithium + PCI as Measured by Total Hippocampal Volume
Time frame: Baseline through 12 months
Number of Participants With Brain Metastases
Time frame: 12 months
Number of Central Nervous System (CNS) Adverse Events
Time frame: Through 12 months
Rate of Overall Survival
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clifford Robinson, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lithium Carbonate and Prophylactic cranial irradiation in people with Small Cell Lung Carcinoma, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2018.