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Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma (B-TREUH)

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ClinicalTrials.gov Identifier: NCT03787303
Recruitment Status : Recruiting
First Posted : December 25, 2018
Last Update Posted : March 22, 2019
Sponsor:
Information provided by (Responsible Party):
Shruti Trehan MD, Aultman Health Foundation

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).

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Thyroid Dysfunction Drug: Triiodothyronine (T3) Phase 2

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.


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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)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.



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Ages Eligible for Study:   18 Years to 105 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Contacts
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Contact: Mary Amos, RN, CCRC 330-363-4162 mary.amos@aultman.com
Contact: Kathleen Collins, RN 330-363-1250 kathleen.collins@aultman.com

Locations
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United States, Ohio
Aultman Medical Group Hematology and Oncology Recruiting
Canton, Ohio, United States, 44710
Contact: Mary Amos, RN, CCRC    330-363-4162    mary.amos@aultman.com   
Contact: Kathleen Collins, RN    330-363-1250    kathleen.collins@aultman.com   
Sub-Investigator: Suzanne Cheng, MD         
Sponsors and Collaborators
Aultman Health Foundation
Investigators
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Principal Investigator: Shruti Trehan, MD Aultman Health Foundation

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Responsible Party: Shruti Trehan MD, Aultman Health Foundation
ClinicalTrials.gov Identifier: NCT03787303     History of Changes
Other Study ID Numbers: 2018.08.ST
First Posted: December 25, 2018    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases