Restoring sensitivity to radioactive iodine in advanced thyroid cancer

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

This study is testing if combining a drug called imatinib with radioactive iodine can help people with advanced thyroid cancer that no longer responds to iodine treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AHS Cancer Control Alberta (Academic / other)
• Drugs / interventions: radiation, Imatinib
• Locations: 1 site (Edmonton, Alberta)
• Trial ID: NCT03469011 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to explore a new treatment approach for patients with advanced papillary thyroid cancer that has become resistant to radioactive iodine therapy. The study will combine the use of imatinib, a drug known to block certain growth factors, with radioactive iodine to potentially restore the cancer cells' ability to uptake the iodine. By targeting the dedifferentiation process that makes these cancer cells less responsive, the trial seeks to determine if this combination can lead to a clinically relevant response in patients. The trial will involve 18 participants over a treatment phase of approximately three months.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed papillary thyroid cancer that is radioiodine-refractory and not amenable to curative surgery or radiation.

Not a fit: Patients with thyroid cancer that is not papillary or follicular, or those who have not experienced radioiodine-refractory disease, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with advanced thyroid cancer who currently have limited options.

How similar studies have performed: While this approach is novel, previous studies have shown promise in using targeted therapies to enhance the effectiveness of traditional treatments in various cancers.

Eligibility criteria

Inclusion Criteria:

* 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:
  1. an index metastatic lesion that was not radioiodine-avid on diagnostic radioiodine scanning performed within 28 days of enrolment;
  2. 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
  3. 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.

     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.

     Exclusion Criteria:
* 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:
  1. Has a documented left ventricular (LV) ejection fraction \< 50%;
  2. Long QT syndrome or family history of long QT syndrome;
  3. Clinically significant resting bradycardia (\<50 bpm);
  4. 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.

Where this trial is running

Edmonton, Alberta

• Cross Cancer Institute — Edmonton, Alberta, Canada (Recruiting)

Study contacts

• Principal investigator: Todd McMullen — Alberta Health services
• Study coordinator: Todd McMullen

Conditions Papillary Thyroid Cancer