Neuroendocrine Tumors
Conditions
Keywords
low-grade neuroendocrine tumors, lithium
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.
Interventions
DRUGLithium 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.
Sponsors
National Institutes of Health (NIH)
National Cancer Institute (NCI)
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Rate Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 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) | 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. |
Countries
United States
Participant flow
Recruitment details
This study enrolled participants with low grade neuroendocrine tumors (NETs) from July 2007 through May 2009.
Participants by arm
| Arm | Count |
|---|---|
| Lithium Lithium carbonate was dosed on a flat scale of mg/day and not by weight or body surface area (BSA). Lithium carbonate was provided as a 300mg tablet and was taken daily without breaks in treatment.
Lithium Carbonate: Lithium 300mg PO TID escalating to a lithium level of 0.8-1.2. Lithium carbonate was administered the first week at 300 mg flat dose three times each day. A serum lithium level was checked after 4-5 days of treatment by drawing a blood sample prior to the morning dose of lithium. Evaluated every 8 weeks. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
Baseline characteristics
| Characteristic | Lithium |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 2 / 15 |
Outcome results
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.
Time frame: Up to 4 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lithium | Tumor Response Rate Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | Complete Response (CR) | 0 participants |
| Lithium | Tumor Response Rate Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | Partial Response (PR) | 0 participants |
| Lithium | Tumor Response Rate Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | Progressive Disease (PD) | 0 participants |
| Lithium | Tumor Response Rate Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | Stable Disease (SD) | 8 participants |
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.
Time frame: Up to 4 years
Population: The median OS time had not been reached.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lithium | Overall Survival (OS) | NA participants |
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.
Time frame: Up to 4 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lithium | Progression Free Survival (PFS) | 4.50 months |