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

February 26, 2012 updated by: David Gius, MD, PhD, Vanderbilt-Ingram Cancer Center

A Phase I Study of Lithium During Whole Brain Radiotherapy for Patients With Brain Metastases

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt-Ingram Cancer Center
      • Nashville, Tennessee, United States, 37064
        • Vanderbilt-Ingram Cancer Center - Cool Springs
      • Nashville, Tennessee, United States, 37064
        • Vanderbilt-Ingram Cancer Center at Franklin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SUPPORTIVE_CARE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Therapeutic Intervention
Procedure: quality-of-life assessment
quality-of-life assessment
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 Names:
  • lithium
Procedure: cognitive assessment
cognitive 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Safety is measured by the rate of grade 3 or worse

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt-Ingram Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Bo Lu, MD, PhD, Vanderbilt-Ingram Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2006

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

May 3, 2007

First Submitted That Met QC Criteria

May 3, 2007

First Posted (Estimate)

May 7, 2007

Study Record Updates

Last Update Posted (Estimate)

February 28, 2012

Last Update Submitted That Met QC Criteria

February 26, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VICC RAD 0521
  • VU-VICC-RAD-0521
  • VU-IRB-051043

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Solid Tumor

Clinical Trials on quality-of-life assessment

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lebanon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe