Differentiated Thyroid Carcinoma, Thyroid Cancer
Conditions
Keywords
Thyroid Neoplasm, I-131, Radiation Dose, Radiation Effect, Pharmaceutical Adjuvant, Thyroid Cancer
Brief summary
This study will examine the safety and effectiveness of using lithium, which has been used to enhance the effectiveness of high-dose 131I, with a single low dose (30 mCi) of 131I for thyroid ablation in patients with recently diagnosed papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid. Participants are randomly assigned to receive lithium capsules or placebo (look-alike capsules with no active ingredient). They follow a low-iodine diet for 2 weeks before starting treatment and are then admitted to the NIH Clinical Center for study and treatment for 11 days, during which they remain on the low-iodine diet. Blood samples are collected almost every day to analyze thyroid hormones, kidney and liver function, lithium concentrations and other tests.
Detailed description
Postsurgical thyroid remnant ablation with (131)I is considered standard clinical care for most cases of papillary and follicular thyroid cancer, to eliminate normal thyroid tissue which may contain microscopic cancer. Furthermore, ablation enhances the sensitivity of subsequent (131)I scanning and serum thyroglobulin (TG) measurement for the detection of recurrent or persistent disease. Low dose (131)I (30 mCi) successfully ablates thyroid remnant in 8-61% of cases. This dose can be repeated and result in overall less radiation exposure than that associated with high dose therapy (100 mCi). Ablation achieved with one or more small doses of radioactive iodine is not associated with decreased survival or cancer recurrence. According to the literature there is no difference in the 30-year recurrence rates between groups receiving low and high dose ablation therapy for well differentiated thyroid cancer without distant metastases at the time of initial therapy. The benefits of using low dose of (131)I are minimization of whole body radiation exposure, reduction in side effects and lower cost. Higher rates of successful ablation by low dose of 131I could be achieved by increasing uptake of (131)I and/or lengthening retention of radioiodine in the remnant thyroid tissue. Recombinant human thyroid-stimulating hormone (rhTSH) has been used successfully to increase radioiodine uptake. Lithium has been used to increase radioiodine retention and has been shown to be useful in the treatment of residual or metastatic cancer. The combination of rhTSH and lithium as adjuncts to 30 mCi radioactive iodine (RAI) ablation therapy in low risk thyroid cancer patients may provide a method that reduces the cumulative dose of radioiodine needed to successfully treat thyroid cancer. The specific aim of this study is to determine whether adjunct lithium carbonate improves the success rate of postsurgical ablation of thyroid remnants using low dose (131)I (30 mCi) and rhTSH in low risk patients with differentiated thyroid carcinoma. Patients with well-differentiated papillary or follicular thyroid cancer stage I or II, according to the National Thyroid Cancer Treatment Cooperative Study (NTCTCS) classification at time of surgery, will be enrolled. Eligible patients will have had a total or near-total thyroidectomy within 6 months of enrollment. This randomized, placebocontrolled, double-blind study will permit an evaluation of the risk/benefit ratio of adding lithium as an adjuvant to the already established method of administering low-dose (131)I ablation therapy, to optimize the (131)I retention. All patients will undergo diagnostic rhTSH (123)I whole body scan at the end of the study to assess the success of thyroid ablation.
Interventions
DRUGLithium Carbonate
30 mCi of 131I
DRUGPlacebo
Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive placebo (look-alike capsules with no active ingredient).
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA 1. Patients older than 16 years with well-differentiated papillary or follicular thyroid cancer stage I or II, according to the NTCTCS classification at time of surgery 2. Patients younger than 45 years with any size of primary papillary or follicular tumor 3. Patients older than 45 years with: 1. primary papillary tumor less than 4 cm or 2. primary follicular tumor less than 1 cm *
Exclusion criteria
1. Patients with postsurgical thyroid remnant more than 5 g 2. Patients with distant metastases 3. Patients above 45 years of age having: 1. known cervical lymph nodes metastases 2. microscopic multifocal follicular cancer 3. microscopic extraglandular invasion of follicular cancer 4. gross extraglandular invasion of papillary or follicular cancer 4. Patients with confirmed histological subtypes of well-differentiated thyroid cancer such as Hurtle cell carcinoma, insular and tall cell variants of papillary cancer. 5. Pregnant or lactating women 6. Patients with renal impairment defined as repeat serum creatinine concentrations above 1.5 mg/dl on thyroid hormone 7. Patients on chronic lithium therapy for psychiatric illness 8. Patients with current unstable cardiovascular conditions 9. Patients with severe chronic medical conditions (liver failure, severe debilitation, dehydration, sodium depletion, any other cancer requiring therapy, etc)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Rate of Successful Thyroid Ablation as Defined by Negative Recombinant Human Thyrotropin (rhTSH) Stimulated Radioiodine Whole Body Scan (RAI WBS) at 1 Year. | 1 year |
Countries
United States
Participant flow
Recruitment details
87 patients were screened for the eligibility for this study. Total of 34 patients were enrolled into the study
Pre-assignment details
The sample size for the trial is 100 patients and the goal for the number of patients to be randomized by November 2010 is 74 patients.
Participants by arm
| Arm | Count |
|---|---|
| Lithium Carbonate Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive lithium capsules. | 15 |
| Placebo Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive placebo (look-alike capsules with no active ingredient). | 14 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 2 | 3 |
Baseline characteristics
| Characteristic | Lithium Carbonate | Placebo | Total |
|---|---|---|---|
| Age Continuous | 39.8 years STANDARD_DEVIATION 11.8 | 38.6 years STANDARD_DEVIATION 10.2 | 39.2 years STANDARD_DEVIATION 10.9 |
| Race/Ethnicity, Customized African American | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 12 Participants | 13 Participants | 25 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 15 participants | 14 participants | 29 participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 1 / 14 |
Outcome results
Primary
The Rate of Successful Thyroid Ablation as Defined by Negative Recombinant Human Thyrotropin (rhTSH) Stimulated Radioiodine Whole Body Scan (RAI WBS) at 1 Year.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lithium Carbonate | The Rate of Successful Thyroid Ablation as Defined by Negative Recombinant Human Thyrotropin (rhTSH) Stimulated Radioiodine Whole Body Scan (RAI WBS) at 1 Year. | 10 Participants |
| Placebo | The Rate of Successful Thyroid Ablation as Defined by Negative Recombinant Human Thyrotropin (rhTSH) Stimulated Radioiodine Whole Body Scan (RAI WBS) at 1 Year. | 10 Participants |