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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests imatinib, a drug that may help treat advanced thyroid cancer by resensitizing cancer cells to radioactive iodine. The focus is on cases where thyroid cancer has spread and no longer responds to standard treatments. Researchers aim to block a specific protein, allowing imatinib to enable radioactive iodine to effectively target and shrink the cancer. The trial seeks participants with papillary thyroid cancer that has not responded to radioactive iodine treatments and cannot be surgically removed. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking certain medications, specifically strong CYP3A4 inhibitors and inducers, before starting the study drug. If you are on medications that prolong the QT interval, you should discuss with your doctor about switching or monitoring with ECG tests.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Studies have shown that imatinib, the drug tested in this trial, has been used safely in treating other types of cancer. For example, past research with patients who had advanced thyroid cancer found that side effects were common but usually mild to moderate. This suggests that while some side effects might occur, they are often not serious. Additionally, imatinib is already approved for treating other cancers like leukemia, providing some confidence about its safety for humans. Although this trial focuses on thyroid cancer, past studies suggest that the drug is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Imatinib is unique because it targets specific proteins involved in the growth of cancer cells, which is different from most current treatments for advanced thyroid cancer that often involve surgery, radioactive iodine, or chemotherapy. Unlike these standard treatments, imatinib works by inhibiting the activity of certain tyrosine kinases, enzymes that play a crucial role in the signaling pathways that promote cancer cell proliferation. Researchers are excited about imatinib because it offers a more targeted approach, potentially minimizing damage to healthy cells and reducing side effects compared to traditional therapies. Additionally, the oral administration of imatinib makes it more convenient for patients, potentially improving adherence to the treatment regimen.

What evidence suggests that imatinib might be an effective treatment for advanced thyroid cancer?

Research has shown that imatinib can help control or reduce tumors in some cancers. Specifically, it stopped tumor growth in 84% of patients and reduced tumor size in 16% of cases for certain advanced cancers. In this trial, participants will receive escalating doses of imatinib to evaluate its effectiveness for advanced thyroid cancer. Although imatinib has not significantly shrunk tumors in medullary thyroid cancer, it has helped some patients maintain stable disease. The drug blocks a protein called PDGFRα, which is believed to aid thyroid cancer growth and resistance to regular treatments. By blocking this protein, imatinib might restore the effectiveness of standard treatments, offering hope for patients with advanced thyroid cancer that has spread beyond the neck. ^{1 6 7 8 9}

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+

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0039606005007221

Cellular effects of imatinib on medullary thyroid cancer ...

Imatinib therapy yielded no objective responses and induced considerable toxicity in patients with MTC. A minority of patients had stable disease.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/17656601/

Efficacy of imatinib mesylate in advanced medullary thyroid ...

Conclusion: Imatinib mesylate is well tolerated, no tumour remission was observed, only transient stable disease was achieved in some patients with advanced MTC ...

3.

journals.sagepub.com

journals.sagepub.com/doi/abs/10.1089/thy.2010.0057

A Phase II Study of Imatinib in Patients with Advanced ...

The median time to follow-up was 26 months (ranges 23–30 months). The rate of 6-month progression-free survival was 36% (95% confidence interval, 9%–65%). The ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4055302/

Imatinib: A Breakthrough of Targeted Therapy in Cancer - PMC

Treatment with Imatinib was successful in stabilizing tumor growth (84%) or shrinking tumor size (16%) in a cohort of patients with progressing, advanced ...

5.

academic.oup.com

academic.oup.com/jcem/article/89/5/2127/2844267

Imatinib Mesylate (Gleevec; STI571) Monotherapy Is ...

Imatinib monotherapy has been highly effective in treating CML patients, with complete remission seen in most patients in the early stages of the disease (5), ...

6.

isrctn.com

isrctn.com/pdf/13256080

A phase II study to investigate the effect of Glivec® ( ...

To evaluate the safety profile of Glivec® in advanced medullary thyroid carcinoma. Overall study start date. 11/07/2003. Completion date. 11/07/2006.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03469011?term=AREA%5BIdSearch%5D(%22NCT03469011%22OR%22NCT00354523%22OR%22NCT00115739%22)&rank=1

A Study to Try to Bring Back Radioiodine Sensitivity in ...

To demonstrate that imatinib can restore iodine uptake in iodine-refractory thyroid carcinoma, as determined by whole body iodine scans. 3 months. Secondary ...

8.

etj.bioscientifica.com

etj.bioscientifica.com/view/journals/etj/10/2/ETJ509457.xml

Benefits and Limitations of TKIs in Patients with Medullary ...

Although promising, these drugs show only a modest effect on advanced thyroid cancer, while they exhibit significant toxicity [8].

9.

rarediseaseadvisor.com

rarediseaseadvisor.com/therapies/gleevec-imatinib/

Gleevec - Imatinib

Although, adverse events occurred frequently, these were mostly mild or moderate. Study findings suggested that 400 mg of imatinib was as ...