NCT03787303: B-TREUH

Study of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma

Terminated Phase 2 Results posted Last updated 13 May 2022

What this trial tests

Phase 2 trial testing Triiodothyronine (T3) in Metastatic Breast Cancer in 7 participants. Terminated before completion.

Timeline

1 March 2019

Primary endpoint
9 March 2022

9 March 2022

Quick facts

Lead sponsor	Aultman Health Foundation
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	7
Start date	1 March 2019
Primary completion	9 March 2022
Estimated completion	9 March 2022
Sites	1 location across United States

Drugs / interventions tested

• Triiodothyronine (T3) — full drug profile →

Conditions studied

• Metastatic Breast Cancer — all drugs for Metastatic Breast Cancer →
• Thyroid Dysfunction — all drugs for Thyroid Dysfunction →

Sponsor

Aultman Health Foundation

Who can join

Adults 18 to 105, any sex, with Metastatic Breast Cancer or Thyroid Dysfunction. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Progression-free Survival at 12 Months Based Upon Clinical and Radiological Assessments Completed as Part of Routine Care Primary · 12 months

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.

Group	Value	95% CI
Triiodothyronine (T3)	4

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

To quantitate the prevalence of hypothyroidism in metastatic breast cancer patients at a community oncology practice.

Group	Value	95% CI
Triiodothyronine (T3)	26

Measurement of Quality of Life Total Score Across Time Using Validated FACT-B Questionnaire Secondary · Baseline, 3, 6, 9, and 12 months

Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score comprised of Physical Well Being (PWB), Social Well Being (SWB), Emotional Well Being (EWB), Functional Well Being (FWB), and Breast Cancer Subscale (BCS). Range is 0-148. A higher score indicates higher quality of life. Missing scores were handled by prorating values.

Baseline

Group	Value	95% CI
Triiodothyronine (T3)	114	± 24.56

At 3 months

Group	Value	95% CI
Triiodothyronine (T3)	114	± 16.80

At 6 months

Group	Value	95% CI
Triiodothyronine (T3)	116	± 20.71

At 9 months

Group	Value	95% CI
Triiodothyronine (T3)	112	± 26.92

At 12 months

Group	Value	95% CI
Triiodothyronine (T3)	110	± 23.68

Measurement of Energy Level Across Time Using FACT-B Question. Secondary · Baseline, 3, 6, 9, 12 months

Functional Assessment of Cancer Therapy - Breast (FACT-B) Lack of energy on 5 point Likert scale as measured on FACT-B Physical Well-being subscale. Score of 0 indicates no lack of energy with score of 4 indicating total lack of energy.

Baseline

Group	Value	95% CI
Triiodothyronine (T3)	2.9	± 1.07

3 months

Group	Value	95% CI
Triiodothyronine (T3)	2.4	± 1.3

6 months

Group	Value	95% CI
Triiodothyronine (T3)	3.0	± 1.16

9 months

Group	Value	95% CI
Triiodothyronine (T3)	3.0	± 1.53

12 months

Group	Value	95% CI
Triiodothyronine (T3)	2.6	± 1.14

Time to Achieve Euthyroid Hypothyroxinemia State Secondary · Number of days between initiation of triiodothyronine (T3) and documentation of first normal TSH value for each participant, assessed up to 12 months

To study the average time required to achieve euthyroid hypothyroxinemia state in qualifying patients. Thyroid function laboratory testing was performed at baseline and then at every 4 weekly intervals until 12 weeks then every 3 monthly thereafter, unless thyroid-stimulating hormone (TSH) was abnormal. If a normal TSH level was not achieved by the 12 week visit, repeat TSH measurements were ordered every 4-6 weeks until the TSH value was within the laboratory normal reference range. Initial euthyroid state defined by number of days between initiation of triiodothyronine (T3) and documentation

Group	Value	95% CI
Triiodothyronine (T3)	59.6	± 50.64

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data was collected for each subject at every 3 monthly visit and is reported as below. Attribution or etiology under comments below. Study period was 12 months (9 months for last patient due to premature termination of study). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Triiodothyronine (T3)

Serious: 2/7 (29%)

Deaths: 1/7

Serious adverse events (3 terms)

Reaction	System	Triiodothyronine (T3)
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—
Cellulitis	Infections and infestations	—
ascites	Gastrointestinal disorders	—

Other adverse events (67 terms — click to expand)

Reaction	System	Triiodothyronine (T3)
Hypertension	Vascular disorders	—
Fatigue	General disorders	—
Hyperglycemia	Metabolism and nutrition disorders	—
Memory Impairment	Nervous system disorders	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Dizziness	Nervous system disorders	—
Neutrophil count decreased	Investigations	—
White blood cell count decreased	Investigations	—
Lymphocyte count decrease	Investigations	—
Nail changes	Skin and subcutaneous tissue disorders	—
Dyspepsia	Gastrointestinal disorders	—
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	—
Diarrhea	Gastrointestinal disorders	—
Abdominal pain	Gastrointestinal disorders	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—
Weight loss	Investigations	—
Headache	Nervous system disorders	—
Chills	General disorders	—
Fever	General disorders	—
Arthalgia	Musculoskeletal and connective tissue disorders	—
Pain	General disorders	—
Skin disorder: Other-onycholysis	Skin and subcutaneous tissue disorders	—
Anemia	Blood and lymphatic system disorders	—
Platelet count decreased	Investigations	—
Hypoalbuminemia	Metabolism and nutrition disorders	—
Alkaline phosphatase increased	Investigations	—
Edema limbs	General disorders	—
Bronchial infection	Infections and infestations	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—
Insomnia	Psychiatric disorders	—
Bloating	Gastrointestinal disorders	—
Gastrointestinal disorder: Other hemoccult positive	Gastrointestinal disorders	—
Sinus tachycardia	Cardiac disorders	—
Bruising	Injury, poisoning and procedural complications	—
Skin disorder other: Contact dermatitis	Skin and subcutaneous tissue disorders	—
Endocrine disorder: Cold intolerance	Endocrine disorders	—
Gastrointestinal disorders: Other - Gastroenteritis	Gastrointestinal disorders	—
Non-cardiac chest pain	General disorders	—

Most-reported serious reactions: Pleural effusion, Cellulitis, ascites.

Data from ClinicalTrials.gov NCT03787303 adverse events section.

Sponsor's own 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).

Publications & conference data

No peer-reviewed publications indexed yet for this trial.