Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma

Metastatic Breast Cancer Clinical Trial

— B-TREUH  

Official title:

A Single Arm Phase II Pilot Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03787303
• Other study ID #: 2018.08.ST
• Status: Terminated
• Phase: Phase 2
• Start date: March 1, 2019
• Est. completion date: March 9, 2022

Study information

• Verified date: May 2022
• Source: Aultman Health Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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 Triiodothyronine (T3) and elevated Thyroid-Stimulating Hormone (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 hypothyroxinemia.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: March 9, 2022
• Est. primary completion date: March 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 105 Years

Eligibility

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, New York Heart Association (NYHA) advanced [Class III/IV] congestive heart failure, 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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer
• Thyroid Dysfunction

Intervention

Drug:
• Triiodothyronine (T3)
Participants will have their L-thyroxine (T4) discontinued and Triiodothyronine (T3)/liothyronine sodium initiated at 3: 1 and titrated.

Locations

Country	Name	City	State
United States	Aultman Medical Group Hematology and Oncology	Canton	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Aultman Health Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Progression-free Survival at 12 Months Based Upon Clinical and Radiological Assessments Completed as Part of Routine Care	To prospectively evaluate the progression-free survival in hypothyroid patients with metastatic breast carcinoma who are rendered euthyroid and hypothyroxinemic. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the nadir sum of the longest diameter (SLD) of target lesions, or unequivocal progression (overall level of substantial worsening) in existing non-target lesions, or the appearance of one or more new lesions.	12 months
Secondary	Number of Patients With Both Metastatic Breast Cancer and Hypothyroidism in All Screened Patients.	To quantitate the prevalence of hypothyroidism in metastatic breast cancer patients at a community oncology practice.	Study duration, planned was 48 months but actual was 36 months [March 1, 2019 to March 9, 2022] due to premature closure due to planned relocation of the PI.
Secondary	Measurement of Quality of Life Total Score Across Time Using Validated FACT-B Questionnaire	Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score comprised of Physical Well Being (PWB), Social Well Being (SWB), Emotional Well Being (EWB), Functional Well Being (FWB), and Breast Cancer Subscale (BCS). Range is 0-148. A higher score indicates higher quality of life. Missing scores were handled by prorating values.	Baseline, 3, 6, 9, and 12 months
Secondary	Measurement of Energy Level Across Time Using FACT-B Question.	Functional Assessment of Cancer Therapy - Breast (FACT-B) Lack of energy on 5 point Likert scale as measured on FACT-B Physical Well-being subscale. Score of 0 indicates no lack of energy with score of 4 indicating total lack of energy.	Baseline, 3, 6, 9, 12 months
Secondary	Time to Achieve Euthyroid Hypothyroxinemia State	To study the average time required to achieve euthyroid hypothyroxinemia state in qualifying patients. Thyroid function laboratory testing was performed at baseline and then at every 4 weekly intervals until 12 weeks then every 3 monthly thereafter, unless thyroid-stimulating hormone (TSH) was abnormal. If a normal TSH level was not achieved by the 12 week visit, repeat TSH measurements were ordered every 4-6 weeks until the TSH value was within the laboratory normal reference range. Initial euthyroid state defined by number of days between initiation of triiodothyronine (T3) and documentation of first normal TSH value.	Number of days between initiation of triiodothyronine (T3) and documentation of first normal TSH value for each participant, assessed up to 12 months