Papillary Thyroid CancerPhase 1NCT03469011
A Study to Try to Bring Back Radioiodine Sensitivity in Patients With Advanced Thyroid Cancer.
A Phase 1 study testing Imatinib Oral Tablet in people with Papillary Thyroid Cancer, run by AHS Cancer Control Alberta at 1 site in Canada.
Trial summary
Thyroid cancers that have spread beyond the neck are not curable. About 30,000 people worldwide die from thyroid cancer every year. Usually, thyroid cancers get worse because the cancer cells become more and more abnormal through a process that is called dedifferentiation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Papillary Thyroid Cancer
- What is being tested?
- Imatinib Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteCanada
- Study dates
- 18 Sep 2018to 31 Jul 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- 1. Cytologically or histologically confirmed papillary thyroid cancer consisting of papillary or follicular variants.
- 2. Radioiodine-refractory disease (iodine-refractory thyroid cancer) by at least one of the following criteria:
- an index metastatic lesion that was not radioiodine-avid on diagnostic radioiodine scanning performed within 28 days of enrolment;
- a radioiodine-avid metastatic lesion that remained stable in size or progressed despite radioiodine treatment 3 months or more before entry into the study; or
- 18F-fluorodeoxyglucose (FDG)-avid lesions on PET scan (if available). 3. Recurrent, advanced, or metastatic (Stage IV) disease that is not amenable to surgical resection or radiation with curative intent.
- 4. Minimal or no radioactive iodine uptake demonstrated by whole body iodine scans.
Show all 12Show fewer
- 5. Age ≥ 18. 6. Eastern Cooperative Oncology (ECOG) performance status of ≤ 1. 7. Presence of measurable disease, defined as at least 1 unidimensional measurable lesion on a computed tomography (CT) scan as defined by RECIST 1.1.
- 8. Hematology: WBC ≥ 3.0 x 109/L or granulocytes (polymorphs + bands) ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L within 4 weeks prior to enrolment.
- 9. AST (SGOT) and/or ALT (SGPT) and alkaline phosphatase ≤ 5 x the upper limit of normal (ULN). Creatinine ≤ 1.5 x ULN.
- 10. Serum amylase and lipase ≤ 1.5 x ULN 11. Serum potassium, phosphorus, magnesium and calcium ≥ lower limit of normal or correctable with supplements prior to first dose of study drug.
- 12. Be able to comply with study procedures and follow-up examinations. 13. Not pregnant or lactating. Male and female patients who are fertile must agree to use an effective means of birth control (i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy.
- 14. Sign a written informed consent.
Who cannot join
- 1. Has received radiation therapy within 21 days of Study Day 1. 2. Has had major surgery within 21 days of Study Day 1. 3. Has untreated brain or meningeal metastases. Patients who have treated brain metastasis (via local radiation standards or surgical resection or local ablative techniques) and who are either off steroids or on a stable dose of steroids for at least one month (30 days), AND who are off anticonvulsants, AND have radiological documented stability of lesions for at least 3 months may be eligible. Each case should be discussed with the Principal Investigator.
- 4. Has a central thoracic tumor lesion as defined by location within the hilar structures.
- 5. Has proteinuria CTCAE v.4.0 Grade > 1 at baseline. 6. Has a history of, or currently exhibits clinically significant cancer related events of bleeding.
- 7. Currently exhibits untreated, symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure (BP) > 90 mm Hg or systolic BP > 140 mm Hg.
- 8. Has a history of myocardial infarction, stroke or Transient Ischemic Attack (TIA) within 6 months of Study Day 1.
- 9. Impaired cardiac function including any of the following:
Show all 19Show fewer
- Has a documented left ventricular (LV) ejection fraction < 50%;
- Long QT syndrome or family history of long QT syndrome;
- Clinically significant resting bradycardia (<50 bpm);
- Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, unstable angina, significant ventricular or atrial tachyarrhythmia).
- 10. Treatment with strong CYP3A4 inhibitors (e.g. erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
- 11. Treatment with strong CYP3A4 inducers (e.g. dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort), and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
- 12. Patients using medication that have been documented to prolong QT interval should be avoided. In the case it is not possible to avoid or switch to other medication, patients should be followed with caution and ECG testing should be requested at least every 3 months after starting study or if any dose change occurs or if clinical symptoms appear.
- 13. Has known autoimmune disease with renal involvement (e.g. lupus). 14. Receiving combination anti-retroviral therapy for HIV. 15. Has clinically significant uncontrolled condition(s). 16. Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix or uterus or non-melanoma skin cancer or in-situ carcinoma of the prostate (Gleason score ≤ 7, with all treatment being completed 6 months prior to enrollment, unless at least 5 years have elapsed since last treatment and the patient is considered cured).
- 17. Has active ulcerative colitis, Crohn's disease, celiac disease, short gut syndrome from any cause, or any other conditions that interfere with absorption.
- 18. History of acute pancreatitis within one year of study entry or medical history of chronic pancreatitis.
- 19. Has a medical condition, which in the opinion of the study investigator places them at an unacceptably high risk for toxicities.
- 20. Pregnant or breast feeding. 21. History of non-compliance to medical regimens or inability to grant consent.
- 22. Use of an investigational agent within 28 days prior to enrollment in the study or foreseen use of an investigational agent during the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Dose Escalation Trial to Determine if Imatinib Treatment Restores Sodium Iodide Symporter Function and Sensitivity to Radioiodine Treatment in Metastatic Thyroid Cancer Patients
Thyroid cancers that have spread beyond the neck are not curable. About 30,000 people worldwide die from thyroid cancer every year. Usually, thyroid cancers get worse because the cancer cells become more and more abnormal through a process that is called dedifferentiation.
Radioactive iodine is a standard treatment for this type of thyroid cancer. Patients will usually receive multiple dose of radioactive iodine over the course of their cancer journey. Thyroid cancers lose sensitivity to radioactive iodine as the cancer progresses/worsens with the process of dedifferentiation. When this occurs, the radioactive iodine treatments no longer work against the cancer and the cancer grows.
Read more
Radioactive iodine enters cancer cells through transporter proteins on the outside of the cancer cell. The transporter proteins that are the most important are the sodium iodide symporters. As thyroid cancers dedifferentiate, these symporters stop working as well as they once did. The radioactive iodine can therefore not get into the cancer cells to cause cancer cell death.
Laboratory research has shown that in thyroid cancer, a protein on the cell called platelet derived growth factor receptor alpha (PDGFRα) is an important for tumour growth and thyroid cancer dedifferentiation. PDGFRα helps cancer progression and lowers the ability of sodium iodine symporters to move radioiodine into cells where it would normal act to kill the cancer cells. PDGFRα therefore makes thyroid cells resistant to radioactive iodine.
Imatinib is an anti-cancer drug that blocks PDGFRα function. It has been used for many years to treat other cancers such as leukemia. The investigators who wrote this study believe that, base on laboratory testing, if thyroid cancer patients are given imatinib whenafter their cancers have become resistant to radioactive iodine, the imatinib will block PDGFRα. This will let the sodium iodine symporters work again and move the radioactive iodine into the cancer cells. This should shrink the tumours. Imatinib would then make the thyroid cancer cell sensitive to radioactive iodine again. This should shrink the tumours and would mean longer control of the cancer, helping people with this disease live longer.
Read the detailed description
This proposed new method of therapy for patients with progressive, metastatic papillary or follicular thyroid cancers will combine a focused blockade of PDGFRα with radioactive iodine. This is based on a new model for dedifferentiation in thyroid cancer as recently published by Lopez-Campistrous et al., 2016 (Appendix 1). Using this model and extensive preclinical data, the investigators hypothesize that the relatively short course of the well-known drug imatinib will allow for re-differentiation of thyroid cancers permitting radioactive iodine transport thus restoring sensitivity to radioactive iodine. The efficacy of these agents will be determined in a trial of 18 patients through a short treatment phase of approximately 3 months through which the investigators should be able to determine a clinically relevant response. The investigators believe this trial is highly clinically relevant and has the benefits of using previously well described treatments in a novel pattern that should maximize efficacy while minimizing toxicity. If successful, this trial will translate into a new treatment paradigm for metastatic thyroid cancer.
- Conditions
- Papillary Thyroid Cancer
- Being tested
- Imatinib Oral Tablet
- Medical subject headings
- Thyroid Cancer, Papillary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib Oral TabletDrug
Also called Gleevec
3+3 trial design. Cohorts of 3-6 patients with escalating imatinib doses. No intra-patient dose escalation allowed.
| Study group | Role | What they receive |
|---|---|---|
| Imatinib oral100mg tablets | Experimental | A standard 3+3 trial design will be utilized for the imatinib dosing. In general, patients will be treated in cohorts of 3-6 with escalating doses of imatinib using oral 100mg tablets.
Dose Level -1=100mg, +1=200mg (starting dose for cohort 1), +2=300mg, +3=400mg, +4=600mg (if needed). Receives: Drug: Imatinib Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Restore iodine uptake
To demonstrate that imatinib can restore iodine uptake in iodine-refractory thyroid carcinoma, as determined by whole body iodine scans.
Measured: 3 months
Secondary outcomes (1)
Decrease overall tumor burden
To determine if treatment with imatinib and radioactive iodine ablation can decrease overall tumor burden through restored sodium iodide symporter function in iodine-refractory thyroid carcinoma. This will be assessed by thyroglobulin levels and by anatomic imaging.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2018
- Study start18 Sep 2018
- Primary completion31 Jul 2024
- Study completion31 Jul 2024
Why it stopped: Lack of Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Papillary Thyroid CancerStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- AHS Cancer Control Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Alberta Cancer Foundation
- Responsible party
- Sponsor
- Investigators
- Todd McMullen, Principal investigator, Alberta Health servicesJennifer Spratlin, MD FRCPC, Principal investigator, Alberta Health services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03469011
- Sponsor's protocol ID
- Imatinib-CCI-PH1-01
- Status last verified
- Jun 2025
- First submitted
- 12 Mar 2018
- Last updated
- 27 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Trial to Determine if Imatinib Treatment Restores Sodium Iodide Symporter Function and Sensitivity to Radioiodine Treatment in Metastatic Thyroid Cancer Patients
- ClinicalTrials.gov ID
- NCT03469011
- Acronym / sponsor ID
- Imatinib-CCI-PH1-01
- Conditions
- Papillary Thyroid Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of Accrual
- Enrolment
- 14 participants (actual)
- Lead sponsor
- AHS Cancer Control AlbertaUniversity, hospital or other
- Collaborators
- Alberta Cancer Foundation
- Study start
- 18 Sep 2018 (actual)
- Primary completion
- 31 Jul 2024 (actual)
- Study completion
- 31 Jul 2024 (actual)
- First posted
- 19 Mar 2018 (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.
Thyroid cancers that have spread beyond the neck are not curable. About 30,000 people worldwide die from thyroid cancer every year. Usually, thyroid cancers get worse because the cancer cells become more and more abnormal through a process that is called dedifferentiation.
Radioactive iodine is a standard treatment for this type of thyroid cancer. Patients will usually receive multiple dose of radioactive iodine over the course of their cancer journey. Thyroid cancers lose sensitivity to radioactive iodine as the cancer progresses/worsens with the process of dedifferentiation. When this occurs, the radioactive iodine treatments no longer work against the cancer and the cancer grows.
Radioactive iodine enters cancer cells through transporter proteins on the outside of the cancer cell. The transporter proteins that are the most important are the sodium iodide symporters. As thyroid cancers dedifferentiate, these symporters stop working as well as they once did. The radioactive iodine can therefore not get into the cancer cells to cause cancer cell death.
Laboratory research has shown that in thyroid cancer, a protein on the cell called platelet derived growth factor receptor alpha (PDGFRα) is an important for tumour growth and thyroid cancer dedifferentiation. PDGFRα helps cancer progression and lowers the ability of sodium iodine symporters to move radioiodine into cells where it would normal act to kill the cancer cells. PDGFRα therefore makes thyroid cells resistant to radioactive iodine.
Imatinib is an anti-cancer drug that blocks PDGFRα function. It has been used for many years to treat other cancers such as leukemia. The investigators who wrote this study believe that, base on laboratory testing, if thyroid cancer patients are given imatinib whenafter their cancers have become resistant to radioactive iodine, the imatinib will block PDGFRα. This will let the sodium iodine symporters work again and move the radioactive iodine into the cancer cells. This should shrink the tumours. Imatinib would then make the thyroid cancer cell sensitive to radioactive iodine again. This should shrink the tumours and would mean longer control of the cancer, helping people with this disease live longer.
Detailed description
This proposed new method of therapy for patients with progressive, metastatic papillary or follicular thyroid cancers will combine a focused blockade of PDGFRα with radioactive iodine. This is based on a new model for dedifferentiation in thyroid cancer as recently published by Lopez-Campistrous et al., 2016 (Appendix 1). Using this model and extensive preclinical data, the investigators hypothesize that the relatively short course of the well-known drug imatinib will allow for re-differentiation of thyroid cancers permitting radioactive iodine transport thus restoring sensitivity to radioactive iodine. The efficacy of these agents will be determined in a trial of 18 patients through a short treatment phase of approximately 3 months through which the investigators should be able to determine a clinically relevant response. The investigators believe this trial is highly clinically relevant and has the benefits of using previously well described treatments in a novel pattern that should maximize efficacy while minimizing toxicity. If successful, this trial will translate into a new treatment paradigm for metastatic thyroid cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imatinib oral100mg tablets | Experimental | Drug: Imatinib Oral TabletA standard 3+3 trial design will be utilized for the imatinib dosing. In general, patients will be treated in cohorts of 3-6 with escalating doses of imatinib using oral 100mg tablets. Dose Level -1=100mg, +1=200mg (starting dose for cohort 1), +2=300mg, +3=400mg, +4=600mg (if needed). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 1. Cytologically or histologically confirmed papillary thyroid cancer consisting of papillary or follicular variants.
- 2. Radioiodine-refractory disease (iodine-refractory thyroid cancer) by at least one of the following criteria:
- 4. Minimal or no radioactive iodine uptake demonstrated by whole body iodine scans.
- 5. Age ≥ 18. 6. Eastern Cooperative Oncology (ECOG) performance status of ≤ 1. 7. Presence of measurable disease, defined as at least 1 unidimensional measurable lesion on a computed tomography (CT) scan as defined by RECIST 1.1.
- 8. Hematology: WBC ≥ 3.0 x 109/L or granulocytes (polymorphs + bands) ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L within 4 weeks prior to enrolment.
Key exclusion criteria (19 listed)
- 1. Has received radiation therapy within 21 days of Study Day 1. 2. Has had major surgery within 21 days of Study Day 1. 3. Has untreated brain or meningeal metastases. Patients who have treated brain metastasis (via local radiation standards or surgical resection or local ablative techniques) and who are either off steroids or on a stable dose of steroids for at least one month (30 days), AND who are off anticonvulsants, AND have radiological documented stability of lesions for at least 3 months may be eligible. Each case should be discussed with the Principal Investigator.
- 4. Has a central thoracic tumor lesion as defined by location within the hilar structures.
- 5. Has proteinuria CTCAE v.4.0 Grade > 1 at baseline. 6. Has a history of, or currently exhibits clinically significant cancer related events of bleeding.
- 7. Currently exhibits untreated, symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure (BP) > 90 mm Hg or systolic BP > 140 mm Hg.
- 8. Has a history of myocardial infarction, stroke or Transient Ischemic Attack (TIA) within 6 months of Study Day 1.
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 |
|---|---|---|
| Imatinib Oral TabletAlso: Gleevec3+3 trial design. Cohorts of 3-6 patients with escalating imatinib doses. No intra-patient dose escalation allowed. | Drug | Imatinib oral100mg tablets |
Primary outcome
Restore iodine uptake
Time frame: 3 months
To demonstrate that imatinib can restore iodine uptake in iodine-refractory thyroid carcinoma, as determined by whole body iodine scans.
1 secondary outcome
Decrease overall tumor burden
Time frame: 3 months
Results and safety
The study was stopped early (reason given: Lack of Accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2025.
- Individual participant dataSharing planned: No
Related trials for Papillary Thyroid Cancer
RecruitingObservational study
Definition of Mutational Profile of Papillary Thyroid Tumors by Mass-ARRAY
Papillary Thyroid Cancer
Not yet recruitingObservational study
Serum Treg/Th17-Related Cytokines and Systemic Inflammatory Indices in Differentiated Thyroid Cancer
Differentiated Thyroid Cancer (DTC), Papillary Thyroid Carcinoma
RecruitingObservational study
Studies on Tumors of the Thyroid
Hurthle Cell Thyroid Cancer, Tall Cell Variant Thyroid Cancer
Active, not recruitingPhase 3
A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy
Differentiated Thyroid Cancer
Not yet recruiting
Personalized Cancer Support (Thrive Track) to Manage the Emotional Needs of Young Adults With Thyroid, Melanoma and Testicular Cancer, PerCS-YA Trial
Differentiated Thyroid Gland Carcinoma, Malignant Testicular Neoplasm
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. This study is not recruiting at the moment.
Todd McMullen principal investigator
Alberta Health services
Jennifer Spratlin, MD FRCPC principal investigator
Alberta Health services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Imatinib Oral Tablet in people with Papillary Thyroid Cancer, run by AHS Cancer Control Alberta at 1 site in Canada.
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 12 inclusion and 19 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: stopped early, as of the sponsor's last update on 27 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of Accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Restore iodine uptake (time frame: 3 months). 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 27 Jun 2025.