Trial record 1 of 1 for:    NCT01553916
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Neuroprotective Effects of Lithium in Patients With Small Cell Lung Cancer Undergoing Radiation Therapy to the Brain

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01553916
First received: March 12, 2012
Last updated: August 12, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Small Cell Lung Carcinoma
Drug: Lithium Carbonate
Phase 1
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 26
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)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01553916

Contacts
Contact: Clifford Robinson, M.D. 314-362-4633 crobinson@radonc.wustl.edu
Contact: Regina Smith 314-454-7986 smithr1@wudosis.wustl.edu

Locations
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.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Clifford Robinson, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01553916     History of Changes
Other Study ID Numbers: 201202073
Study First Received: March 12, 2012
Last Updated: August 12, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lithium
Lithium Carbonate
Antidepressive Agents
Antimanic Agents
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 23, 2014