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

Phase 1

Terminated

• Conditions: Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Neurotoxicity; Solid Tumor
• Interventions: Drug: lithium carbonate; Procedure: cognitive assessment; Procedure: quality-of-life assessment; Radiation: radiation therapy

• Registration Number: NCT00469937
• Lead Sponsor: Vanderbilt-Ingram Cancer Center

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.

Study Timeline

• Study Start: 2006-02
• Study First Submitted: 2007-05-03
• Study First Submitted QC: 2007-05-03
• Study First Posted: 2007-05-07
• Primary Completion: 2009-03
• Study Completion: 2009-03
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-26
• Last Update Posted: 2012-02-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Therapeutic Intervention	lithium carbonate	-
Therapeutic Intervention	cognitive assessment	-
Therapeutic Intervention	quality-of-life assessment	-
Therapeutic Intervention	radiation therapy	-

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (3)

Vanderbilt-Ingram Cancer Center - Cool Springs; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center at Franklin; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States