Description:
Up to one third of breast cancer patients have hypothyroidism or hyperthyroidism. L-thyroxine
(T4), or Synthroid, is the most commonly prescribed agent for the management of
hypothyroidism in the US. However, there are data suggesting that triiodothyronine (T3) may
have benefits in preventing disease progression over l-thyroxine (T4).
Title
- Brief Title: Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma
- Official Title: A Single Arm Phase II Pilot Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma
Clinical Trial IDs
- ORG STUDY ID:
2018.08.ST
- NCT ID:
NCT03787303
Conditions
- Metastatic Breast Cancer
- Thyroid Dysfunction
Interventions
| Drug | Synonyms | Arms |
|---|
| Triiodothyronine (T3) | liothyronine sodium | Triiodothyronine (T3) |
Purpose
Up to one third of breast cancer patients have hypothyroidism or hyperthyroidism. L-thyroxine
(T4), or Synthroid, is the most commonly prescribed agent for the management of
hypothyroidism in the US. However, there are data suggesting that triiodothyronine (T3) may
have benefits in preventing disease progression over l-thyroxine (T4).
Detailed Description
It is estimated that there are approximately 155,000 living with metastatic breast cancer in
the US and the number is estimated to increase over the next years (SEER data). Although
their median survival has improved over the last 2 decades from 17 months to approximately 24
months attributed to newer treatments, there is an ongoing need for additional strategies and
research to improve survival and quality of life.
Many studies have explored the connection between hypothyroidism and hyperthyroidism and
breast cancer with varied results ranging up to one third prevalence. Low T3 and elevated TSH
levels have been detected in newly diagnosed breast cancer patients. Other studies have
suggested that some of the common symptoms reported by breast cancer survivors such as
fatigue and depression can be attributed to subclinical hypothyroidism.
L-thyroxine (T4) is the most commonly prescribed agent for the management of hypothyroidism
in the US. However, there are data suggesting that T4 is a potent pro-oncogenic agent.
Proposed mechanisms include stimulation of mitogenesis, angiogenesis and resistance to
apoptosis, opposition of anti-PDL-1 and radiation effects. It has been postulated that the
avbeta3integrin that is universally expressed on cancer cells harbors a thyroid hormone
receptor and T4 interacts with it.
Triiodothyronine (T3) on the other hand, is significantly less oncogenic and less mitogenic
and is downstream of T4 which is a T3 pro-hormone. Therefore, exogenous supplementation of T3
would decrease the T4 levels creating the desired state of euthyroid hypothyroxiemia.
The rationale of this study is to replace L-thyroxine (T4) with Triiodothyronine (T3) in
hypothyroid patients with metastatic breast carcinoma while they continue to receive standard
systemic therapy, titrating the dose to achieve a state of euthyroid hypothyroxinemia which
is turn would result in a lower risk of disease progression and improved survival by lowering
the concentration of T4.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Triiodothyronine (T3) | Experimental | Following discontinuation of L-thyroxine (T4), triiodothyronine (T3) will be initiated at a 3:1 ratio. The dose will be titrated by the investigator to maintain levels of free T4 < 50% of normal range while maintaining a euthyroid state. Triiodothyronine (T3) tablets for oral administration will be prescribed once or twice daily depending on the total dose. Treatment duration will be approximately 9 months during which time the subjects will continue to be treated and monitored as usual for their metastatic breast cancer. During the study period and at the conclusion of the study period, there will be continuous evaluations of the disease status and thyroid status with the option of resuming the original thyroid replacement or continuation of the triiodothyronine (T3). | |
Eligibility Criteria
Inclusion Criteria:
- Age greater than or equal to 18
- Male or female with diagnosis of metastatic breast carcinoma and documented history of
hypothyroidism .
- TSH level within normal range at baseline
- Life expectancy estimated > 3 months
- Ability and willingness to provide informed consent
Exclusion Criteria:
- Life expectancy estimated to be less than 3 months
- Is currently pregnant or intends to become pregnant during the duration of the study
- Active angina, NYHA advanced [Class III/IV] CHF, or uncontrolled cardiac arrhythmia
within 6 months of enrollment
- History of thyrotoxicosis
- History of adrenal insufficiency
- Hypersensitivity to any active or extraneous constituents in Triiodothyronine
(T3)/liothyronine sodium
| Maximum Eligible Age: | 105 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progression-free survival based upon clinical and radiological assessments completed as part of routine care |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | To prospectively evaluate the progression-free survival in hypothyroid patients with metastatic breast carcinoma who are rendered euthyroid and hypothyroxinemic. |
Secondary Outcome Measures
| Measure: | Prevalence of hypothyroidism in metastatic breast cancer patients of all screened patients. |
| Time Frame: | Study duration, anticipated 48 months |
| Safety Issue: | |
| Description: | To quantitate the prevalence of hypothyroidism in metastatic breast cancer patients. |
| Measure: | Measurement of quality of life using validated FACT-B questionnaire |
| Time Frame: | 0, 3, 6, 9, 12 months |
| Safety Issue: | |
| Description: | Monitor Quality of Life using FACT-B Questionnaire |
| Measure: | Time to achieve euthyroid hypothyroxinemia state |
| Time Frame: | Study duration, anticipated 12 months |
| Safety Issue: | |
| Description: | To prospectively study the feasibility and average time required to achieve the euthyroid hypothyroxinemia state in qualifying patients. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Aultman Health Foundation |
Last Updated
July 20, 2021
