Brain and Central Nervous System Tumors, Cognitive/Functional Effects, Neurotoxicity, Solid Tumor
Conditions
Keywords
radiation toxicity, neurotoxicity, cognitive/functional effects, unspecified adult solid tumor, protocol specific, adult tumors metastatic to brain
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.
Interventions
DRUGlithium 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
PROCEDUREcognitive assessment
cognitive assessment
PROCEDUREquality-of-life assessment
quality-of-life assessment
RADIATIONradiation 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.
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility of concurrent lithium carbonate and whole-brain radiotherapy as measured by safety and compliance | Safety is measured by the rate of grade 3 or worse |
Countries
United States
Outcome results
None listed