Ph I Study of Lithium During Whole Brain Radiotherapy For Patients With Brain Metastases
This study has been terminated.
(low accrual)
Sponsor:
Vanderbilt-Ingram Cancer Center
Collaborator:
Information provided by (Responsible Party):
David Gius, MD, PhD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00469937
First received: May 3, 2007
Last updated: February 26, 2012
Last verified: February 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors Cognitive/Functional Effects Neurotoxicity Solid Tumor |
Drug: lithium carbonate Procedure: cognitive assessment Procedure: quality-of-life assessment Radiation: radiation therapy |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Supportive Care |
| Official Title: | A Phase I Study of Lithium During Whole Brain Radiotherapy for Patients With Brain Metastases |
Resource links provided by NLM:
Further study details as provided by Vanderbilt-Ingram Cancer Center:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: Yes ]
| Enrollment: | 9 |
| Study Start Date: | February 2006 |
| Study Completion Date: | March 2009 |
| Primary Completion Date: | March 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Therapeutic Intervention |
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 Name: lithium
Procedure: cognitive assessment
cognitive assessment
Other Name: cognitive assessment
Procedure: quality-of-life assessment
quality-of-life assessment
Other Name: quality-of-life 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.
Other Name: radiation therapy
|
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| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00469937
Locations
| United States, Tennessee | |
| Vanderbilt-Ingram Cancer Center - Cool Springs | |
| Nashville, Tennessee, United States, 37064 | |
| Vanderbilt-Ingram Cancer Center at Franklin | |
| Nashville, Tennessee, United States, 37064 | |
| Vanderbilt-Ingram Cancer Center | |
| Nashville, Tennessee, United States, 37232-6838 | |
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
| Principal Investigator: | Bo Lu, MD, PhD | Vanderbilt-Ingram Cancer Center |
More Information
No publications provided
| Responsible Party: | David Gius, MD, PhD, Professor; Radiation Oncologist, Vanderbilt-Ingram Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00469937 History of Changes |
| Other Study ID Numbers: | VICC RAD 0521, VU-VICC-RAD-0521, VU-IRB-051043 |
| Study First Received: | May 3, 2007 |
| Last Updated: | February 26, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Vanderbilt-Ingram Cancer Center:
|
radiation toxicity neurotoxicity cognitive/functional effects unspecified adult solid tumor, protocol specific adult tumors metastatic to brain |
Additional relevant MeSH terms:
|
Neoplasm Metastasis Nervous System Neoplasms Central Nervous System Neoplasms Neurotoxicity Syndromes Neoplastic Processes Neoplasms Pathologic Processes Neoplasms by Site Nervous System Diseases Poisoning Substance-Related Disorders Lithium Lithium Carbonate |
Antipsychotic Agents Tranquilizing Agents Central Nervous System Depressants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Psychotropic Drugs Antimanic Agents Antidepressive Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 22, 2013