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

This study has been terminated.
(low accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
David Gius, MD, PhD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00469937
First received: May 3, 2007
Last updated: February 26, 2012
Last verified: February 2012
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Phase I Study of Lithium During Whole Brain Radiotherapy for Patients With Brain Metastases

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: February 2006
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: cognitive assessment
Procedure: quality-of-life assessment
quality-of-life assessment
Other Name: 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.
Other Name: radiation therapy

Detailed Description:

OBJECTIVES:

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

PRIOR CONCURRENT THERAPY:

  • 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
  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: NCT00469937

Locations
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
Investigators
Principal Investigator: Bo Lu, MD, PhD Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: David Gius, MD, PhD, Professor; Radiation Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00469937     History of Changes
Other Study ID Numbers: VICC RAD 0521, VU-VICC-RAD-0521, VU-IRB-051043
Study First Received: May 3, 2007
Last Updated: February 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
radiation toxicity
neurotoxicity
cognitive/functional effects
unspecified adult solid tumor, protocol specific
adult tumors metastatic to brain

Additional relevant MeSH terms:
Neoplasm Metastasis
Nervous System Neoplasms
Central Nervous System Neoplasms
Neurotoxicity Syndromes
Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Site
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Lithium
Lithium Carbonate
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014