Lithium for Low-Grade Neuroendocrine Tumors

Neuroendocrine Tumors Clinical Trial

Official title:

A Phase II Clinical and Biological Study of Lithium Carbonate in Patients With Low-Grade Neuroendocrine Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00501540
• Other study ID #: CO07203
• Secondary ID: R21CA117117-01A2
• Status: Completed
• Phase: Phase 2
• Start date: July 2007
• Est. completion date: June 2009

Study information

• Verified date: March 2017
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neuroendocrine Tumors

Intervention

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.

Locations

Country	Name	City	State
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin

Sponsors (3)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor Response Rate Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)	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.	Up to 4 years
Secondary	Progression Free Survival (PFS)	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.	Up to 4 years
Secondary	Overall Survival (OS)	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.	Up to 4 years

External Links

•   University of Wisconsin Carbone Cancer Center