RAI + Immunotherapy for Thyroid Cancer

Recruiting at 8 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, PD1/PD-L1 inhibitors

Disqualifiers: Autoimmune disease, Pneumonitis, Organ transplant, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

11 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out what effects, good and/or bad, a drug called durvalumab combined with Thyrogen-stimulated RAI, has on the patient and thyroid cancer. Durvalumab is a drug that has been developed to activate the immune system by blocking a protein called programmed death ligand-1 (PD-L1) that can be present on tumor and normal cells, including immune cells.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have had certain treatments like chemotherapy, immunotherapy, or targeted therapy within 28 days before starting the study. It's best to discuss your specific medications with the trial team.

Is the combination of RAI and Durvalumab safe for humans?

Durvalumab, an immune checkpoint inhibitor, can cause side effects like thyroid dysfunction and rare conditions such as hypoparathyroidism (a condition where the parathyroid glands produce too little hormone). These side effects are part of a group called immune-related adverse events, which can affect various organs. ^{1 2 3 4 5}

How is the drug Durvalumab with Radioiodine (RAI) different from other treatments for thyroid cancer?

Durvalumab combined with Radioiodine (RAI) is unique because it integrates immunotherapy, which uses the body's immune system to fight cancer, with traditional radioactive iodine treatment, potentially offering a new approach for patients with thyroid cancer that is resistant to standard RAI therapy. This combination could provide an alternative to the current use of multi-kinase inhibitors, which target specific cancer cell pathways but do not involve the immune system. ^{6 7 8 9 10}

Research Team

Alan L Ho, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with certain types of thyroid cancer that has returned or spread, and who have at least one tumor visible on specific scans. They should be in good physical condition, able to follow the study's procedures including biopsies, and not have had certain recent treatments or conditions like severe allergies to durvalumab or Thyrogen, autoimmune diseases, lung inflammation history, organ transplants, uncontrolled illnesses or brain metastases.

Inclusion Criteria

Patients must agree to undergo two research biopsies of malignant lesions

My thyroid cancer is confirmed and is of a type that started in the follicular cells.

My scans show at least one active cancer spot.

Exclusion Criteria

I have had severe side effects from previous immunotherapy.

I have had an autoimmune disease in the last 2 years.

I have previously been treated with a PD1 or PD-L1 inhibitor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab 1500 mg IV every 4 weeks, with Thyrogen and RAI administered in Cycle 1/Week 3

6 weeks

1 visit every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Durvalumab
• Radioiodine (RAI)

Trial Overview The trial tests the combination of a drug called durvalumab (which boosts the immune system by blocking PD-L1 protein) with radioiodine therapy stimulated by Thyrogen in patients with recurrent/metastatic thyroid cancers. The goal is to assess the effectiveness and safety of this combination treatment.

Participant Groups

Group I: Radioiodine (RAI) in Combination with Durvalumab (Medi4736) Experimental Treatment 2 Interventions

Enrolled patients will be treated with durvalumab 1500 mg IV every 4 weeks. In Cycle 1/Week 3, Thyrogen 0.9 mg IM will be administered on two consecutive calendar days followed by 100 mCi (+/- 10 mCi) of RAI the next calendar day. Durvalumab will be continued every 4 weeks.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

MedImmune LLC

Industry Sponsor

Trials

348

Recruited

788,000+

Founded

1988

Headquarters

Gaithersburg, USA

Known For

Biologics research

Top Products

Synagis, FluMist

Dr. Reginald Seeto

MedImmune LLC

Chief Medical Officer since 2008

MD from University of Sydney, B.Sc. from University of Sydney

Peter Greenleaf

MedImmune LLC

Chief Executive Officer since 2006

MBA from St. Joseph’s University, B.S. from Western Connecticut State University

Findings from Research

Multi-kinase inhibitors (MKIs) significantly improve progression-free survival (PFS) and overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer (RAI-rDTC), with a median PFS hazard ratio of 0.30 and OS hazard ratio of 0.70 based on a meta-analysis of randomized controlled trials.

While MKIs are effective, they are associated with a higher incidence of adverse events compared to control treatments, highlighting the need for careful patient evaluation to balance treatment benefits against potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of multi-kinase inhibitors in patients with radioiodine-refractory differentiated thyroid cancer: a systematic review and meta-analysis of clinical trials. Su, J., Wang, M., Fu, Y., et al.[2022]

Radioiodine (RAI)-refractory thyroid cancer is rare, with a very low 10-year survival rate of less than 10%, particularly affecting older patients and those with aggressive tumor characteristics.

Multikinase inhibitors (MKIs) like sorafenib and lenvatinib have shown promise in improving progression-free survival in patients with RAI-refractory thyroid cancer, but they have not yet demonstrated an overall survival benefit, highlighting the need for careful patient selection and timing of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation. Schmidt, A., Iglesias, L., Klain, M., et al.[2023]

Real-world data confirms that sorafenib and lenvatinib are effective in improving progression-free survival and possibly overall survival in patients with radioiodine-resistant differentiated thyroid carcinomas (RAIR-DTC).

Safety profiles from real-world studies align with clinical trial data, showing manageable adverse events, which supports the use of these multikinase inhibitors as viable treatment options, particularly in second-line settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multikinase inhibitors for the treatment of radioiodine refractory thyroid cancer: what have we learned from the 'real-world' experience? Costante, G.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Hypoparathyroidism: an uncommon adverse effect of treatment with durvalumab. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Rare immune-related adverse events in a patient with metastatic melanoma: a case report highlighting sarcoidosis-like reactions triggered by immune-checkpoint inhibitors. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitor-related New-onset Thyroid Dysfunction: A Retrospective Analysis Using the US FDA Adverse Event Reporting System. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Divergent prognostic effects of pre-existing and treatment-emergent thyroid dysfunction in patients treated with immune checkpoint inhibitors. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of multi-kinase inhibitors in patients with radioiodine-refractory differentiated thyroid cancer: a systematic review and meta-analysis of clinical trials. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Current Standards in Treatment of Radioiodine Refractory Thyroid Cancer. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Differentiated thyroid cancer: focus on emerging treatments for radioactive iodine-refractory patients. [2022]

9. Brazil pubmed.ncbi.nlm.nih.gov

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Multikinase inhibitors for the treatment of radioiodine refractory thyroid cancer: what have we learned from the 'real-world' experience? [2021]