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

Primary Purpose

Brain and Central Nervous System Tumors, Cognitive/Functional Effects, Neurotoxicity

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
lithium carbonate
cognitive assessment
quality-of-life assessment
radiation therapy
Sponsored by
Vanderbilt-Ingram Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Brain and Central Nervous System Tumors focused on measuring radiation toxicity, neurotoxicity, cognitive/functional effects, unspecified adult solid tumor, protocol specific, adult tumors metastatic to brain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Vanderbilt-Ingram Cancer Center - Cool Springs
  • Vanderbilt-Ingram Cancer Center at Franklin
  • Vanderbilt-Ingram Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Therapeutic Intervention

Arm Description

Outcomes

Primary Outcome Measures

Feasibility of concurrent lithium carbonate and whole-brain radiotherapy as measured by safety and compliance

Secondary Outcome Measures

Full Information

First Posted
May 3, 2007
Last Updated
February 26, 2012
Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00469937
Brief Title
Ph I Study of Lithium During Whole Brain Radiotherapy For Patients With Brain Metastases
Official Title
A Phase I Study of Lithium During Whole Brain Radiotherapy for Patients With Brain Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
February 2012
Overall Recruitment Status
Terminated
Why Stopped
low accrual
Study Start Date
February 2006 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors, Cognitive/Functional Effects, Neurotoxicity, Solid Tumor
Keywords
radiation toxicity, neurotoxicity, cognitive/functional effects, unspecified adult solid tumor, protocol specific, adult tumors metastatic to brain

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Therapeutic Intervention
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
lithium carbonate
Other Intervention Name(s)
lithium
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
cognitive assessment
Intervention Description
cognitive assessment
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
Intervention Description
quality-of-life assessment
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
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 Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bo Lu, MD, PhD
Organizational Affiliation
Vanderbilt-Ingram Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt-Ingram Cancer Center - Cool Springs
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37064
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center at Franklin
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37064
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6838
Country
United States

12. IPD Sharing Statement

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

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