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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00469937
• Other study ID #: VICC RAD 0521
• Secondary ID: VU-VICC-RAD-0521
• Status: Terminated
• Phase: Phase 1
• First received: May 3, 2007
• Last updated: February 26, 2012
• Start date: February 2006
• Est. completion date: March 2009

Study information

• Verified date: February 2012
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Cognitive/Functional Effects
• Nervous System Neoplasms
• Neurotoxicity
• Neurotoxicity Syndromes
• Solid Tumor

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

Procedure:
• cognitive assessment
cognitive assessment
• quality-of-life assessment
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.

Locations

Country	Name	City	State
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center - Cool Springs	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center at Franklin	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes