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Lithium for Low-Grade Neuroendocrine Tumors

Primary Purpose

Neuroendocrine Tumors

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lithium Carbonate
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroendocrine Tumors focused on measuring low-grade neuroendocrine tumors, lithium

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lithium

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
July 13, 2007
Last Updated
November 14, 2019
Sponsor
University of Wisconsin, Madison
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00501540
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Tumors
Keywords
low-grade neuroendocrine tumors, lithium

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lithium
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Lithium Carbonate
Intervention Description
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.
Primary Outcome Measure Information:
Title
Tumor Response Rate Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)
Description
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.
Time Frame
Up to 4 years
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
Up to 4 years
Title
Overall Survival (OS)
Description
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.
Time Frame
Up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Noelle LoConte, MD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Herbert Chen, MD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Study Chair
Facility Information:
Facility Name
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21393344
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.
Results Reference
result
Links:
URL
https://cancer.wisc.edu/
Description
University of Wisconsin Carbone Cancer Center

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Lithium for Low-Grade Neuroendocrine Tumors

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