Clinical Trials /

Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma

NCT03787303

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
Triiodothyronine (T3)liothyronine sodiumTriiodothyronine (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

NameTypeDescriptionInterventions
Triiodothyronine (T3)ExperimentalFollowing 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).
  • 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 15, 2020