Clinical trial NCT03787303: Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma
Official title: A Single Arm Phase II Pilot Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Thyroid Dysfunction
Lead sponsor: Aultman Health Foundation
Sponsor class: OTHER
First posted: 2018-12-26
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 105
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Triiodothyronine (T3) - IND Exempt
Primary purpose: TREATMENT

Brief 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).

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 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.

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, 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

Primary outcomes:
measure: Number of Participants With Progression-free Survival at 12 Months Based Upon Clinical and Radiological Assessments Completed as Part of Routine Care
timeFrame: 12 months
Secondary outcomes:
measure: Number of Patients With Both Metastatic Breast Cancer and Hypothyroidism in All Screened Patients.
timeFrame: 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.
measure: Measurement of Quality of Life Total Score Across Time Using Validated FACT-B Questionnaire
timeFrame: Baseline, 3, 6, 9, and 12 months
measure: Measurement of Energy Level Across Time Using FACT-B Question.
timeFrame: Baseline, 3, 6, 9, 12 months
measure: Time to Achieve Euthyroid Hypothyroxinemia State
timeFrame: Number of days between initiation of triiodothyronine (T3) and documentation of first normal TSH value for each participant, assessed up to 12 months
Other outcomes:
Locations:
city: Canton
country: United States
facility: Aultman Medical Group Hematology and Oncology
state: Ohio
Study officials:
affiliation: Aultman Health Foundation
name: Shruti Trehan, MD
role: PRINCIPAL_INVESTIGATOR
References: