Imatinib for Advanced Thyroid Cancer

Overseen By Todd McMullen

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AHS Cancer Control Alberta

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Untreated brain metastases, Uncontrolled hypertension, Heart disease, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3 months

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Who Is on the Research Team?

Todd McMullen

Principal Investigator

Alberta Health services

Jennifer Spratlin, MD FRCPC

Principal Investigator

Alberta Health services

Are You a Good Fit for This Trial?

This trial is for adults with advanced papillary thyroid cancer that has spread and no longer responds to radioiodine treatment. Participants must have a certain level of blood cell counts, normal organ function tests, and be able to follow the study plan. Pregnant or breastfeeding individuals are excluded, as well as those with other significant health issues or recent treatments that could affect safety.

Inclusion Criteria

You have thyroid cancer that does not respond to radioiodine treatment according to specific criteria.

You have cancer that has come back, spread, or is in an advanced stage that cannot be treated with surgery or radiation to cure it.

Age ≥ 18

Exclusion Criteria

Received radiation therapy within 21 days of Study Day 1

Had major surgery within 21 days of Study Day 1

You have a medical condition that makes it very risky for you to take the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of imatinib to restore iodine uptake in thyroid cancer

3 months

Cohorts of 3-6 patients with dose escalation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Imatinib

Trial Overview The trial is testing Imatinib Oral Tablet's ability to restore sensitivity to radioiodine in thyroid cancer cells by blocking PDGFRα protein function. This could potentially shrink tumors and improve disease control in patients whose cancers have become resistant to standard radioactive iodine therapy.

How Is the Trial Designed?

Group I: Imatinib oral100mg tablets Experimental Treatment 1 Intervention

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).

Imatinib is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Gleevec for:

• Chronic myeloid leukemia
• Gastrointestinal stromal tumors
• Dermatofibrosarcoma protuberans
• Systemic mastocytosis
• Hypereosinophilic syndrome

Approved in United States as Gleevec for:

• Chronic myeloid leukemia
• Gastrointestinal stromal tumors
• Dermatofibrosarcoma protuberans
• Systemic mastocytosis
• Hypereosinophilic syndrome

Approved in Canada as Glivec for:

• Chronic myeloid leukemia
• Gastrointestinal stromal tumors
• Dermatofibrosarcoma protuberans
• Systemic mastocytosis
• Hypereosinophilic syndrome

Approved in Japan as Glivec for:

• Chronic myeloid leukemia
• Gastrointestinal stromal tumors
• Dermatofibrosarcoma protuberans
• Systemic mastocytosis
• Hypereosinophilic syndrome

Approved in Switzerland as Gleevec for:

• Chronic myeloid leukemia
• Gastrointestinal stromal tumors
• Dermatofibrosarcoma protuberans
• Systemic mastocytosis
• Hypereosinophilic syndrome

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Alberta Cancer Foundation

Collaborator

Trials

18

Recruited

5,600+