Clinical trial NCT00469937: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-05-07
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Feasibility of concurrent lithium carbonate and whole-brain radiotherapy as measured by safety and compliance
timeFrame: Safety is measured by the rate of grade 3 or worse
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center - Cool Springs
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Franklin
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Bo Lu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: