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

Vanderbilt University Medical Center

Status and phase

Terminated

Phase 1

Conditions

Solid Tumor

Brain and Central Nervous System Tumors

Neurotoxicity

Cognitive/Functional Effects

Treatments

Procedure: quality-of-life assessment

Procedure: cognitive assessment

Drug: lithium carbonate

Radiation: radiation therapy

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00469937

VU-IRB-051043

VICC RAD 0521

VU-VICC-RAD-0521

Details and patient eligibility

About

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.

Full 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.

Enrollment

9 patients

Sex

All

Ages

18+ years old

Volunteers

No 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