A Study to Try to Bring Back Radioiodine Sensitivity in Patients With Advanced Thyroid Cancer.
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|ClinicalTrials.gov Identifier: NCT03469011|
Recruitment Status : Recruiting
First Posted : March 19, 2018
Last Update Posted : January 10, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Papillary Thyroid Cancer||Drug: Imatinib Oral Tablet||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||September 18, 2018|
|Estimated Primary Completion Date :||January 31, 2020|
|Estimated Study Completion Date :||June 30, 2020|
Experimental: Imatinib oral100mg tablets
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).
Drug: Imatinib Oral Tablet
3+3 trial design. Cohorts of 3-6 patients with escalating imatinib doses. No intra-patient dose escalation allowed.
Other Name: Gleevec
- 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.
- Decrease overall tumor burden [ Time Frame: 3 months ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03469011
|Contact: Todd McMullen||780-407-1108||Todd.Mcmullen@albertahealthservices.ca|
|Contact: Jennifer Spratlin, MD FRCPC||780-432-8514||Jennifer.Spratlin@albertahealthservices.ca|
|Cross Cancer Institute||Recruiting|
|Edmonton, Alberta, Canada|
|Contact: Todd McMullen|
|Principal Investigator:||Todd McMullen||Alberta Health Services|
|Principal Investigator:||Jennifer Spratlin, MD FRCPC||Alberta Health Services|