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Ph I Study of Lithium During Whole Brain Radiotherapy For Patients With Brain Metastases

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ClinicalTrials.gov Identifier: NCT00469937
Recruitment Status : Terminated (low accrual)
First Posted : May 7, 2007
Last Update Posted : February 28, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
David Gius, MD, PhD, Vanderbilt-Ingram Cancer Center

Brief Summary:

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as lithium, may protect normal cells from the side effects of radiation therapy. Giving lithium together with radiation therapy may allow a higher dose of radiation therapy to be given so that more tumor cells are killed.

PURPOSE: This phase I trial is studying the side effects and best dose of lithium when given together with whole-brain radiation therapy in treating patients with brain metastases from primary cancer outside the brain.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Cognitive/Functional Effects Neurotoxicity Solid Tumor Drug: lithium carbonate Procedure: cognitive assessment Procedure: quality-of-life assessment Radiation: radiation therapy Phase 1

Detailed Description:


  • Determine the feasibility of concurrent lithium carbonate and whole-brain radiotherapy, as measured by safety and compliance, in patients with primary extracranial malignancy and brain metastases.

OUTLINE: This is an open-label, dose-escalation study of lithium carbonate.

Patients receive oral lithium carbonate twice daily on days 1-7 and 2-4 times daily on days 8-21. Patients undergo whole-brain radiotherapy once daily on days 8-12 and 15-19.

Cohorts of 3-6 patients receive escalating doses of lithium carbonate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Quality of life and mental status are assessed at baseline, on days 1, 8, and 15, at 1-month post-treatment, and then periodically thereafter.

After completion of study treatment, patients are followed at 1 month and then periodically thereafter.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Phase I Study of Lithium During Whole Brain Radiotherapy for Patients With Brain Metastases
Study Start Date : February 2006
Actual Primary Completion Date : March 2009
Actual Study Completion Date : March 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Therapeutic Intervention Drug: lithium carbonate
Dose levels Neoadjuvant lithium Concurrent lithium Dose level -1 300mg po QD 300mg po QD Dose level (starting dose) 300mg po BID 300mg po BID Dose level 2 300mg po TID 300mg po TID Dose level 3 300mg po QID 300mg po QID
Other Name: lithium

Procedure: cognitive assessment
cognitive assessment

Procedure: quality-of-life assessment
quality-of-life assessment

Radiation: radiation therapy
Protocol radiotherapy must begin within seven days following initiation of Lithium therapy if day seven falls on a holiday or weekend; it is acceptable to begin treatment the next business day. One treatment of 3Gy will be given daily with the exception of weekends and holidays for a total of (10 fractions) for a total of 30 Gy over 2 to 3 weeks.

Primary Outcome Measures :
  1. Feasibility of concurrent lithium carbonate and whole-brain radiotherapy as measured by safety and compliance [ Time Frame: Safety is measured by the rate of grade 3 or worse ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histopathologically confirmed extracranial primary malignancy

    • Multiple (i.e., > 3) brain metastases OR < 3 metastases with at least 1 metastasis > 4.0 cm in diameter
    • Not eligible for radiosurgery
  • No requirement for immediate whole-brain radiotherapy
  • No metastases to the midbrain or brainstem

Exclusion Criteria:

  • Zubrod performance status 0-2
  • Life expectancy ≥ 8 weeks
  • Platelet count > 100,000/mm^3
  • ANC > 1,500/mm^3
  • Hemoglobin ≥ 10 g/dL
  • BUN < 25 mg/dL
  • Creatinine < 1.5 mg/dL
  • Bilirubin < 1.5 mg/dL
  • ALT ≤ 2 times normal
  • Sodium > 136 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Neurologically stable

    • No seizure disorders or seizures due to brain metastases
  • No medical illnesses or psychiatric conditions that would preclude completion of study treatment
  • No sensory neuropathy ≥ grade 2
  • No bipolar disorder
  • No thyroid disease
  • No QTc interval prolongation


  • More than 2 weeks since prior and no concurrent chemotherapy
  • At least 2 weeks since prior and no concurrent NSAIDs, angiotensin-converting enzyme inhibitors (e.g., enalapril or captopril), calcium channel blockers, diuretics, selective cyclooxygenase-2 inhibitors, acetazolamide, urea, xanthine, or alkalinizing agents (e.g., sodium bicarbonate)
  • No prior radiotherapy to the head and neck area
  • No prior radiosurgery
  • No concurrent radiotherapy to other sites
  • No concurrent anticonvulsants due to brain metastases
  • No concurrent psychoactive drugs
  • No concurrent thyroid medications
  • No concurrent amifostine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00469937

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United States, Tennessee
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Bo Lu, MD, PhD Vanderbilt-Ingram Cancer Center
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Responsible Party: David Gius, MD, PhD, Professor; Radiation Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00469937    
Other Study ID Numbers: VICC RAD 0521
First Posted: May 7, 2007    Key Record Dates
Last Update Posted: February 28, 2012
Last Verified: February 2012
Keywords provided by David Gius, MD, PhD, Vanderbilt-Ingram Cancer Center:
radiation toxicity
cognitive/functional effects
unspecified adult solid tumor, protocol specific
adult tumors metastatic to brain
Additional relevant MeSH terms:
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Brain Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neurotoxicity Syndromes
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Chemically-Induced Disorders
Lithium Carbonate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs