Clinical trial NCT00501540: Lithium for Low-Grade Neuroendocrine Tumors
Official title: A Phase II Clinical and Biological Study of Lithium Carbonate in Patients With Low-Grade Neuroendocrine Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Keywords: low-grade neuroendocrine tumors
lithium
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2007-07-16
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to learn more about the effectiveness and side effects of lithium treatment for subjects with low-grade neuroendocrine tumors.

Detailed description: Lithium 300mg by mouth, three times daily, escalating to a lithium level of 0.8-1.0; Continue until progressive disease/unacceptable toxicity;Evaluate q 8 weeks.

Eligibility criteria: Inclusion Criteria:

* Must have histologically confirmed metastatic low-grade neuroendocrine neoplasms. Small cell lung cancers, paragangliomas and pheochromocytomas are excluded. Pathologic diagnosis must be confirmed at the University of Wisconsin Carbone Cancer Center (UWCCC). Grading must be confirmed by pathologic review performed at UWCCC.
* Must have measurable disease
* Must have radiographic evidence of disease progression following any prior systemic therapy, chemoembolization, bland embolization, surgery, or observation.
* Must be ≥ 4 weeks from the completion of major surgery, chemotherapy, or other systemic therapy or local liver therapy to study registration
* Must be ≥ 3 weeks from the completion of radiation therapy to study registration
* The following laboratory values are to be obtained within 14 days prior to registration: Absolute neutrophils count (ANC) ≥ 1000/mm3; Platelets ≥ 75,000/mm3; Hemoglobin ≥ 8.0 g/dL; Total bilirubin less than or equal 2.0 X the upper limit of normal (ULN); AST less than or equal to 3 X ULN or less than or equal 5 X ULN if liver metastases are present; Creatinine less than or equal ULN; Serum sodium within normal limits
* PS = 0-2
* Capable of understanding the investigational nature, potential risks and benefits fo the study and able to provide valid informed consent.
* Must have available tissue specimens to be analyzed for pathologic confirmation.
* Age ≥ 18 years.
* Women must not be pregnant or lactating.
* Women of childbearing potential and sexually active males are required to use an accepted and effective method of contraception.
* Patients must not have known history of allergic reactions or adverse reactions to Lithium or derivatives.
* Patients are not allowed to be on concurrent chemotherapy or radiation therapy.
* Patients are excluded if they have any of the following:

Gastrointestinal tract disease resulting in an inability to take oral medication (i.e. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, bowel obstruction, or inability to swallow the tablets.

History of hypothyroid disease Significant, active cardiac disease

* Patients must not be taking the following medications: diuretics, ACE inhibitors, NSAIDs (except aspirin or sulindac), neuroleptics, tetracycline, COX2 (cyclooxygenase-2) inhibitors, citalopram, clovoxamine, escitalopram, femoxetine, fluoxetine, fluvoxamine, paroxatine, sertraline, and zimeldine.
* Must be willing to undergo a tumor biopsy pre and post therapy.
* Patients with a concurrent malignancy are allowed on study as long as the patient is not undergoing active treatment for their disease.
* Patients already taking Lithium for any reason are not allowed on study.

Primary outcomes:
measure: Tumor Response Rate Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to 4 years
measure: Overall Survival (OS)
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Noelle LoConte, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Herbert Chen, MD
role: STUDY_CHAIR
References:
citation: Lubner SJ, Kunnimalaiyaan M, Holen KD, Ning L, Ndiaye M, Loconte NK, Mulkerin DL, Schelman WR, Chen H. A preclinical and clinical study of lithium in low-grade neuroendocrine tumors. Oncologist. 2011;16(4):452-7. doi: 10.1634/theoncologist.2010-0323. Epub 2011 Mar 10.