Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma

NCT03787303 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2018.08.ST
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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).

Conditions

Metastatic Breast Cancer; Thyroid Dysfunction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of Patients With Both Metastatic Breast Cancer and Hypothyroidism in All Screened Patients.

  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.

• Measurement of Quality of Life Total Score Across Time Using Validated FACT-B Questionnaire

  Baseline, 3, 6, 9, and 12 months

• Measurement of Energy Level Across Time Using FACT-B Question.

  Baseline, 3, 6, 9, 12 months

• Time to Achieve Euthyroid Hypothyroxinemia State

  Number of days between initiation of triiodothyronine (T3) and documentation of first normal TSH value for each participant, assessed up to 12 months

Study Arms (1)

Triiodothyronine (T3)

EXPERIMENTAL

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)

Interventions

Triiodothyronine (T3) DRUG

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

Also known as: liothyronine sodium

Triiodothyronine (T3)

Eligibility Criteria

• Age: 18 Years - 105 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aultman Health Foundation: lead

Study Sites (1)

Aultman Medical Group Hematology and Oncology

Canton, Ohio, 44710, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Triiodothyronine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Thyronines; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Thyroxine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Limitation is small sample size due to pandemic affecting clinical trial accrual. A larger sample is needed to adequately answer the research question.

Results Point of Contact

• Title: Shruti Trehan MD
• Organization: Aultman Hospital

trehanshruti4@gmail.com

3303634162

Study Officials

• Shruti Trehan, MD

  Aultman Health Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: N/A (not applicable)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Shruti Trehan MD

Model Details: Triiodothyronine (T3) - IND Exempt

Study Record Dates

• First Submitted: December 12, 2018
• First Posted: December 26, 2018
• Study Start: March 1, 2019
• Primary Completion: March 9, 2022
• Study Completion: March 9, 2022
• Last Updated: May 13, 2022
• Results First Posted: May 13, 2022

Record last verified: 2022-05

Locations

US (1)