COACH - Comparing Two Different Methods to Suppress Thyrotropin in Patients With Advanced Thyroid Cancer
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAHS Cancer Control Alberta
About this trial
Most thyroid cancers can be cured with surgery, sometimes with radioactive iodine therapy. However, some patients have cancer that has spread, and some have cancer that comes back after treatment. For those with remaining cancer, lowering TSH levels is recommended. This is because thyroid cancer growth can depend on TSH, so reducing TSH can lower the risk of cancer returning and slow its growth in patients with cancer that can't be surgically removed.
International guidelines recommend keeping TSH levels as low as \<0.1 mU/L for patients with advanced thyroid cancer. This advice is based on past studies, but it hasn't been tested in a controlled way. One old study suggested that not lowering TSH enough could lead to more cancer relapses. Another study suggested that lowering TSH more could help prevent cancer from getting worse in high-risk patients. However, a recent study found no link between TSH levels and better outcomes, and the researchers suggested doing a new study to confirm if this practice is truly beneficial.
Lowering TSH levels to \<0.1 mU/L using levothyroxine has been the standard of care for treating advanced thyroid cancer for a long time. The researchers would like to investigate whether using levothyroxine to keep TSH levels between 0.1 and 0.5 mU/L is just as safe and effective for cancer treatment as the current recommendation of keeping it below 0.1 mU/L. The researchers also believe this study can help set TSH suppression targets based on cancer type, reducing unnecessary side effects from too much TSH suppression while still achieving the same cancer treatment results.
If the researchers can prove that keeping TSH levels between 0.1 and 0.5 mU/L is just as safe and effective as the standard of care practice, we can change our standard treatment approach. This would help reduce symptoms for our patients.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Minimum age of 18 years, with no upper limit of age.
ECOG 0-2
Patients must be capable of providing consent to enrollment and willing to comply with study treatment and follow-up.
Diagnosis of differentiated thyroid cancer (including papillary, follicular, oncocytic, and poorly differentiated subtypes) with advanced structural disease (defined as unresectable persistent/ recurrent locoregional disease and/or distant metastases).
Disqualifiers
Recent acute coronary event (within 6 months of randomization).
History of atrial fibrillation.
Known hypersensitivity to levothyroxine.
History of fragility fractures or established diagnosis of osteoporosis.
Trial design
Design model
Parallel
Treatments tested in this trial
Levothyroxine Oral Tablet [Synthroid]
DrugRound, colour coded, scored tablet debossed with "SYNTHROID" on one side and potency on the other side.
Treatment groups
70 Participants
are divided into 2 treatment groupsGroup A: Levothyroxine dosing with a target Thyrotropin (TSH) suppressed level of <0.1 mU/LActive comparator 1 intervention
Group B: Levothyroxine dosing with a target Thyrotropin (TSH) suppressed level of 0.1 - 0.5 mU/LExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Proportion of Patients Who are Alive and Progression-free at One Year
Progression will be defined using RECIST criteria 1.1 and will be based on radiological assessment only. Biomarkers (such as thyroglobulin) will not be considered given the significant limitations associated with these biomarkers in the setting of locally recurrent or metastatic differentiated thyroid cancer.
Time frame
up to 1 year after randomisation.Secondary outcomes
1
Mean Change of Symptom Burden (as assessed by ESAS)
Edmonton Symptom Assessment Score (ESAS) is a standard way of monitoring patient-reported outcomes in all Cancer Care Alberta facilities. Through this system, we will assess the trajectory of symptom burden across preplanned timepoints during the study duration. We will add hyperthyroidism-specific symptoms (e.g., racing heart or palpitations) in the others category of the ESAS form.
Time frame
Screening, 6 months, 12 months, 18 months, 24 months2
Proportion of Patients Who are Alive and Progression-free at One Year According to Molecular Subtype (RAS-like vs BRAF-like cancers)
Cancers with the following molecular changes within initial NGS, will be considered as BRAF-like (BRAF V600E mutation, NTRK fusion, ALK fusion, and RET fusion). Cancers with the following molecular changes will be considered as RAS-like (any RAS mutation, BRAF 601E, PAX 8/PPARG). We will examine if there is a difference in the oncological impact of TSH suppression among patients with BRAF-like tumors vs those with RAS-like tumors (given the clinical and biological differences between these two groups of patients). This outcome will be measured one year after randomization. NGS testing is currently conducted by Alberta Precision Labs and should be funded from the study's budget (for patients who have not had testing already prior to study entry as part of their routine clinical care).
Time frame
1 year after randomization3
Median Progression-free Survival
Progression-free survival is defined as the time from randomization until radiological disease progression or death. Assessment of progression will be based only on RECIST criteria version 1.1.
Time frame
6 months, 12 months or death4
Rate of levothyroxine-related adverse events
We would like to examine the difference between levothyroxine-related adverse events in both groups (including diarrhea, anxiety, psychiatric disorders, cardiac adverse events, among others). We will report all grade adverse events comparing the number of AEs between each group.
Time frame
Screening to End of Study (2 years)Locations
Sponsors and contacts
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Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: