Advanced Differentiated Thyroid Gland CarcinomaPhase 2NCT06790589
COACH - Comparing Two Different Methods to Suppress Thyrotropin in Patients With Advanced Thyroid Cancer
A Phase 2 study testing Levothyroxine Oral Tablet [Synthroid] in people with Advanced Differentiated Thyroid Gland Carcinoma, run by AHS Cancer Control Alberta.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Differentiated Thyroid Gland Carcinoma
- What is being tested?
- Levothyroxine Oral Tablet [Synthroid]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- Dec 2026to Jan 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- Residence within Alberta and referral to the Cross Cancer Institute in Edmonton, for consideration of anticancer therapy and/or follow-up.
- Absence of any condition hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the study.
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- Patients of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period and for a period of 30 days after the last dose of study drug. A highly effective method of birth control is defined as those resulting in low failure rate (i.e., less than 1% per year) when used consistently and correctly.
- Note: abstinence is acceptable if this is established and preferred contraception for the patient.
- Women of childbearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 40 mIU/mL to confirm menopause.
- Females must not be breastfeeding (timeframe: during study treatment period and for a period of 30 days after the last dose of the study drug).
- Ability to obtain sufficient thyroid cancer tissue to conduct baseline NGS testing (could be fresh or archived tissue).
Who cannot join
- Recent acute coronary event (within 6 months of randomization).
- History of atrial fibrillation.
- Known hypersensitivity to levothyroxine.
- Treatment with other investigational drugs within 30 days prior to randomization.
- History of fragility fractures or established diagnosis of osteoporosis.
- Prior treatment with levothyroxine before study entry at any dose and with any TSH target is not an exclusion criterion.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: COmparison of Two Alternative Thyrotropin Suppression Strategies Among Patients With Advanced Differentiated Cancer of the tHyroid
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.
Read more
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.
- Being tested
- Levothyroxine Oral Tablet [Synthroid]
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Levothyroxine Oral Tablet [Synthroid]Drug
Round, colour coded, scored tablet debossed with "SYNTHROID" on one side and potency on the other side.
| Study group | Role | What they receive |
|---|---|---|
| Levothyroxine dosing with a target Thyrotropin (TSH) suppressed level of <0.1 mU/L | Active comparator | Levothyroxine oral tablet treatment daily with doses optimized to achieve an initial target TSH level of <0.1 mU/L for a total of two years. Receives: Drug: Levothyroxine Oral Tablet [Synthroid] |
| Levothyroxine dosing with a target Thyrotropin (TSH) suppressed level of 0.1 - 0.5 mU/L | Experimental | Levothyroxine oral tablet treatment daily with doses optimized to achieve an initial target TSH level of 0.1-0.5 mU/L for a total of two years. Receives: Drug: Levothyroxine Oral Tablet [Synthroid] |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 1 year after randomisation.
Secondary outcomes (4)
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.
Measured: Screening, 6 months, 12 months, 18 months, 24 months
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).
Measured: 1 year after randomization
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.
Measured: 6 months, 12 months or death
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.
Measured: Screening to End of Study (2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2025
- Study startDec 2026 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionJan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Differentiated Thyroid Gland CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AHS Cancer Control Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Omar Abdelsalam, Principal investigator, Cross Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06790589
- Sponsor's protocol ID
- IIT-0033
- Status last verified
- Feb 2026
- First submitted
- 9 Jan 2025
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COmparison of Two Alternative Thyrotropin Suppression Strategies Among Patients With Advanced Differentiated Cancer of the tHyroid
- ClinicalTrials.gov ID
- NCT06790589
- Acronym / sponsor ID
- IIT-0033
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- AHS Cancer Control AlbertaUniversity, hospital or other
- Study start
- Dec 2026 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Jan 2031 (estimated)
- First posted
- 24 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levothyroxine dosing with a target Thyrotropin (TSH) suppressed level of <0.1 mU/L | Active comparator | Drug: Levothyroxine Oral Tablet [Synthroid]Levothyroxine oral tablet treatment daily with doses optimized to achieve an initial target TSH level of <0.1 mU/L for a total of two years. |
| Levothyroxine dosing with a target Thyrotropin (TSH) suppressed level of 0.1 - 0.5 mU/L | Experimental | Drug: Levothyroxine Oral Tablet [Synthroid]Levothyroxine oral tablet treatment daily with doses optimized to achieve an initial target TSH level of 0.1-0.5 mU/L for a total of two years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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).
- Residence within Alberta and referral to the Cross Cancer Institute in Edmonton, for consideration of anticancer therapy and/or follow-up.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Levothyroxine Oral Tablet [Synthroid]Round, colour coded, scored tablet debossed with "SYNTHROID" on one side and potency on the other side. | Drug | Levothyroxine dosing with a target Thyrotropin (TSH) suppressed level of 0.1 - 0.5 mU/L, Levothyroxine dosing with a target Thyrotropin (TSH) suppressed level of <0.1 mU/L |
Primary outcome
Proportion of Patients Who are Alive and Progression-free at One Year
Time frame: up to 1 year after randomisation.
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.
4 secondary outcomes
Mean Change of Symptom Burden (as assessed by ESAS)
Time frame: Screening, 6 months, 12 months, 18 months, 24 months
Proportion of Patients Who are Alive and Progression-free at One Year According to Molecular Subtype (RAS-like vs BRAF-like cancers)
Time frame: 1 year after randomization
Median Progression-free Survival
Time frame: 6 months, 12 months or death
Rate of levothyroxine-related adverse events
Time frame: Screening to End of Study (2 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Omar Abdelsalam principal investigator
Cross Cancer Institute
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Levothyroxine Oral Tablet [Synthroid] in people with Advanced Differentiated Thyroid Gland Carcinoma, run by AHS Cancer Control Alberta.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Omar Abdelsalam (780-432-8290, omar.abdelsalam@ahs.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Patients Who are Alive and Progression-free at One Year (time frame: up to 1 year after randomisation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.