Lithium for Low-Grade Neuroendocrine Tumors

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Neuroendocrine Tumors	Drug: Lithium Carbonate	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	15 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase II Clinical and Biological Study of Lithium Carbonate in Patients With Low-Grade Neuroendocrine Tumors
Study Start Date :	July 2007
Actual Primary Completion Date :	June 2009
Actual Study Completion Date :	June 2009

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Lithium; Lithium carbonate will be dosed on a flat scale of mg/day and not by weight or body surface area (BSA). Lithium carbonate will be provided as a 300mg tablet and will be taken daily without breaks in treatment.	Drug: Lithium Carbonate; Lithium 300mg PO TID escalating to a lithium level of 0.8-1.2. Lithium carbonate will be administered the first week at 300 mg flat dose three times each day. A serum lithium level will be checked after 4-5 days of treatment by drawing a blood sample prior to the morning dose of lithium. Evaluate every 8 weeks.

Outcome Measures

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Primary Outcome Measures :

1. Tumor Response Rate Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 4 years ]
   Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR) >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >=20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), small changes that do not meet the above criteria.

Secondary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: Up to 4 years ]
   Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression free survival is measured from the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression. If a participant did not experience an event of disease progression or death at the time of analysis (03/10/2011), then the patient's data was censored at the date of the last available evaluation.
2. Overall Survival (OS) [ Time Frame: Up to 4 years ]
   Overall survival for a participant is defined as the number of days from the day of first Lithium administration to the participant's death. As of the time of analysis (03/10/2011), median overall survival duration was not reached.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Locations

United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

University of Wisconsin, Madison

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Noelle LoConte, MD	University of Wisconsin, Madison
Study Chair:	Herbert Chen, MD	University of Wisconsin, Madison

More Information

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Responsible Party:	University of Wisconsin, Madison
ClinicalTrials.gov Identifier:	NCT00501540 History of Changes
Other Study ID Numbers:	CO07203; R21CA117117-01A2 ( U.S. NIH Grant/Contract ); 2007-0065 ( Other Identifier: Institutional Review Board ); NCI-2011-00616 ( Registry Identifier: National Cancer Institute Clinical Trial Reporting Program )
First Posted:	July 16, 2007
Results First Posted:	May 3, 2017
Last Update Posted:	May 3, 2017
Last Verified:	March 2017

Keywords provided by University of Wisconsin, Madison:

low-grade neuroendocrine tumors; lithium

Additional relevant MeSH terms:

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Lithium Carbonate; Antidepressive Agents	Psychotropic Drugs; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antimanic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs