Lithium for Low-Grade Neuroendocrine Tumors

• ClinicalTrials.gov Identifier: NCT00501540
• Recruitment Status: Completed
• First Posted: July 16, 2007
• Results First Posted: May 3, 2017
• Last Update Posted: November 26, 2019
• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institutes of Health (NIH); National Cancer Institute (NCI)
• Information provided by (Responsible Party): University of Wisconsin, Madison

Tracking Information

• First Submitted Date: July 13, 2007
• First Posted Date: July 16, 2007
• Results First Submitted Date: December 5, 2016
• Results First Posted Date: May 3, 2017
• Last Update Posted Date: November 26, 2019
• Study Start Date: July 2007
• Actual Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2017)

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.

• Original Primary Outcome Measures (submitted: July 13, 2007): tumor response rate of patients with low-grade neuroendocrine tumors treated with lithium

Current Secondary Outcome Measures (submitted: March 22, 2017)

• 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.
• 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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.

Study Arms

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.

Intervention: Drug: Lithium Carbonate

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 15, 2010): 15
• Original Estimated Enrollment (submitted: July 13, 2007): 33
• Actual Study Completion Date: June 2009
• Actual Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00501540
• Other Study ID Numbers: CO07203; R21CA117117-01A2 ( U.S. NIH Grant/Contract ); H-2007-0065 ( Other Identifier: Institutional Review Board ); NCI-2011-00616 ( Registry Identifier: NCI Trial ID ); A534260 ( Other Identifier: UW Madison ); SMPH\MEDICINE\HEM-ONC ( Other Identifier: UW Madison )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Wisconsin, Madison
• Study Sponsor: University of Wisconsin, Madison

Collaborators

• 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

• PRS Account: University of Wisconsin, Madison
• Verification Date: March 2017