RAI + Immunotherapy for Thyroid Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of combining durvalumab, an immunotherapy drug, with radioiodine (RAI) on thyroid cancer. Durvalumab boosts the immune system by blocking a protein that protects cancer cells. The trial seeks individuals diagnosed with thyroid cancer that has recurred or spread. Participants must have at least one visible area of cancer on a scan. As an Early Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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

Research shows that durvalumab, combined with radioiodine (RAI), is under investigation for safety in treating thyroid cancer. Earlier studies found that patients tolerated durvalumab, although some experienced side effects like tiredness and mild skin reactions.

Durvalumab aids the immune system in attacking cancer cells by blocking a protein that usually inhibits this process. It has been used in other cancer types, but its combination with RAI for thyroid cancer remains under investigation. As this trial is in its early stages, complete safety details for this specific use are not yet available. However, durvalumab's safe use in other treatments suggests it might be well-tolerated here as well.

Overall, while some side effects may occur, existing research offers reassurance about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for thyroid cancer, which typically involve surgery, radioactive iodine (RAI) therapy, and hormone therapy, this new approach combines RAI with durvalumab, an immunotherapy drug. Researchers are excited because durvalumab works by targeting and blocking a protein called PD-L1, which can help the immune system better recognize and attack cancer cells. The combination of enhancing the immune response while using RAI to target thyroid cancer cells could potentially offer a more effective treatment strategy, especially for patients whose cancer is resistant to traditional therapies. This innovative blend of treatments is paving the way for potentially improved outcomes in thyroid cancer care.

What evidence suggests that this trial's treatments could be effective for thyroid cancer?

Research has shown that durvalumab, a drug that boosts the immune system, may help treat various types of cancer. It blocks a protein called PD-L1, which cancer cells use to evade the immune system. In this trial, participants will receive a combination of durvalumab with radioiodine (RAI) to enhance the body's ability to fight thyroid cancer. This combination might prove more effective than RAI alone. Early studies on similar combinations suggest possible benefits, but further research is needed to confirm these effects specifically for thyroid cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Alan L Ho, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrial.be clinicaltrial.be/en/details/8656?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

RAI Plus Immunotherapy for Recurrent/Metastatic Thyroid C... The purpose of this study is to find out what effects, good and/or bad, a drug called durvalumab combined with Thyrogen-stimulated RAI, ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35521657/

A Pilot Study of Durvalumab (MEDI4736) with Tremelimumab ... The primary endpoint was 1 year OS with the combination of durvalumab, tremelimumab, and SBRT in metastatic ATC patients with a target of 1 year OS in ≥2 out of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225001641

Effectiveness of immune checkpoint inhibitor therapy in ... Efficacy outcomes. Of the 3 studies that reported BOR, partial response was the best response observed with rates varying by tumour type from 0 ...

4. researchgate.net researchgate.net/publication/360425618_A_Pilot_Study_of_Durvalumab_MEDI4736_with_Tremelimumab_in_Combination_with_Image_Guided_Stereotactic_Body_Radiotherapy_SBRT_in_the_Treatment_of_Metastatic_Anaplastic_Thyroid_Cancer?_tp=eyJjb250ZXh0Ijp7InBhZ2UiOiJzY2llbnRpZmljQ29udHJpYnV0aW9ucyIsInByZXZpb3VzUGFnZSI6bnVsbCwic3ViUGFnZSI6bnVsbH19

A Pilot Study of Durvalumab (MEDI4736) with ... MSI-high patients were on treatment before progression for 8-14 weeks. The median OS was 14.5 weeks with only one person alive beyond 1 year.

5. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03753919

NCT03753919 | Durvalumab Plus Tremelimumab for the ... This is a prospective, multi-centre, open label, stratified, exploratory phase II study evaluating the efficacy and safety of durvalumab plus tremelimumab in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03215095

RAI Plus Immunotherapy for Recurrent/Metastatic Thyroid ... 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12527727/

Immune checkpoint inhibitors against thyroid cancer - PMC While most trials met their primary endpoints, only five reported positive results, involving key drugs such as Pembrolizumab, Lenvatinib, ...

8. cancertreatmentreviews.com cancertreatmentreviews.com/article/S0305-7372(25)00164-1/pdf

Effectiveness of immune checkpoint inhibitor therapy in ... Therefore, this review aims to assess the effectiveness of ICI therapy in adult patients with thyroid cancer, with safety as a secondary outcome ...