Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma

NCT ID: NCT03787303

Last Updated: 2022-05-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-01
• Study Completion Date: 2022-03-09

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.

Conditions

Metastatic Breast Cancer; Thyroid Dysfunction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Triiodothyronine (T3)

Intervention Type: DRUG

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

Interventions

Triiodothyronine (T3)

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

Intervention Type: DRUG

Other Intervention Names

liothyronine sodium

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 105 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aultman Health Foundation

OTHER

Sponsor Role: lead

Responsible Party

Shruti Trehan MD

Shruti Trehan MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shruti Trehan, MD

Role: PRINCIPAL_INVESTIGATOR

Aultman Health Foundation

Locations

Aultman Medical Group Hematology and Oncology

Canton, Ohio, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2018.08.ST

Identifier Type: -

Identifier Source: org_study_id