Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma (B-TREUH)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03787303|
Recruitment Status : Recruiting
First Posted : December 26, 2018
Last Update Posted : July 16, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer Thyroid Dysfunction||Drug: Triiodothyronine (T3)||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Triiodothyronine (T3) - IND Exempt|
|Masking:||None (Open Label)|
|Masking Description:||N/A (not applicable)|
|Official Title:||A Single Arm Phase II Pilot Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma|
|Actual Study Start Date :||March 1, 2019|
|Estimated Primary Completion Date :||January 2023|
|Estimated Study Completion Date :||January 2023|
Experimental: Triiodothyronine (T3)
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).
Drug: Triiodothyronine (T3)
Participants will have their L-thyroxine (T4) discontinued and Triiodothyronine (T3)/liothyronine sodium initiated at 3: 1 and titrated.
Other Name: liothyronine sodium
- Progression-free survival based upon clinical and radiological assessments completed as part of routine care [ Time Frame: 12 months ]To prospectively evaluate the progression-free survival in hypothyroid patients with metastatic breast carcinoma who are rendered euthyroid and hypothyroxinemic.
- Prevalence of hypothyroidism in metastatic breast cancer patients of all screened patients. [ Time Frame: Study duration, anticipated 48 months ]To quantitate the prevalence of hypothyroidism in metastatic breast cancer patients.
- Measurement of quality of life using validated FACT-B questionnaire [ Time Frame: 0, 3, 6, 9, 12 months ]Monitor Quality of Life using FACT-B Questionnaire
- Time to achieve euthyroid hypothyroxinemia state [ Time Frame: Study duration, anticipated 12 months ]To prospectively study the feasibility and average time required to achieve the euthyroid hypothyroxinemia state in qualifying patients.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03787303
|Contact: Mary Amos, RN, CCRCfirstname.lastname@example.org|
|Contact: Kathleen Collins, RNemail@example.com|
|United States, Ohio|
|Aultman Medical Group Hematology and Oncology||Recruiting|
|Canton, Ohio, United States, 44710|
|Contact: Mary Amos, RN, CCRC 330-363-4162 firstname.lastname@example.org|
|Contact: Kathleen Collins, RN 330-363-1250 email@example.com|
|Sub-Investigator: Suzanne Cheng, MD|
|Principal Investigator:||Shruti Trehan, MD||Aultman Health Foundation|