Radiotherapy + Radiopharmaceutical Therapy for Thyroid Cancer

Overseen By Dana B. Kaplin, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Disqualifiers: Pregnancy, Breastfeeding, CNS metastases, others

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

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating thyroid cancer using two types of radiation: radioactive iodine (RAI) and external beam radiotherapy (XRT). The goal is to determine if this combination can safely deliver higher radiation doses to thyroid cancer that has spread and cannot be fully removed by surgery. Researchers aim to assess whether this approach can more effectively tackle the cancer. Individuals with thyroid cancer that did not fully respond to surgery and has spread to other parts of the body might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment approach.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must have adequately recovered from any prior chemotherapy, and any toxicities from previous therapies should have improved to a certain level. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both external beam radiotherapy (XRT) and radioactive iodine (RAI) are generally well-tolerated treatments for thyroid cancer. Studies have found that XRT can significantly shrink tumors in many patients. Most people do not experience serious side effects, though some might have mild to moderate ones.

RAI therapy has been used safely for a long time. Most people do not face a significant increase in overall cancer risk after treatment. However, there is a small chance of developing other types of cancer later, especially for younger patients, though this risk remains very low.

Both treatments are considered safe, but individual experiences can vary. It's important to discuss potential risks and benefits with a healthcare provider to understand what is best for your specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining External Beam Radiotherapy (XRT) with Radioactive Iodine (RAI) for treating high-risk thyroid cancer because this approach could offer a more comprehensive attack on cancer cells. Standard treatments often include surgery and RAI alone, but this combination adds the precision of XRT, which targets and destroys cancer cells externally. By integrating these two methods, there's potential for improved effectiveness in cases where cancer has recurred and isn't fully responsive to surgery. This dual approach may provide hope for better outcomes and fewer recurrences for patients with aggressive thyroid cancer.

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

Research has shown that using external beam radiotherapy (XRT) along with radioactive iodine (RAI) may effectively treat thyroid cancer. In this trial, all participants will receive both XRT and RAI. Studies have found that XRT can shrink tumors in 73% of patients, with many seeing results within six months. It also helps prevent cancer recurrence in the same area. When used after surgery, RAI therapy has demonstrated a high success rate, with some studies showing a 90% remission rate. Together, these treatments can deliver more radiation directly to the tumors, potentially leading to better outcomes for patients with thyroid cancer that is hard to remove. ^{1 2 3 4 6}

Who Is on the Research Team?

Harry Quon, MD

Principal Investigator

Johns Hopkins, School of Medicine, Radiation Oncology

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with well-differentiated thyroid cancer that's spread and can't be fully removed by surgery. They should have a life expectancy of at least 8 weeks, adequate organ function, and a Karnofsky performance status over 50%. Pregnant or breastfeeding individuals, those recently exposed to iodinated contrast, or sexually active premenopausal patients not using contraception are excluded.

Inclusion Criteria

I have recovered from my last chemotherapy with mild or no side effects.

I am able to care for myself but cannot do normal activities or work.

My thyroid cancer has spread to my neck and/or other parts of my body and cannot be fully removed by surgery.

Exclusion Criteria

I have advanced brain metastases or critical lesions in my hip or spine that make certain treatments risky.

Pregnancy or breastfeeding

I have not been exposed to iodinated contrast in the last 6 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combined radioactive iodine (RAI, 131-I) and external beam radiotherapy (XRT) to optimize the radiation dose for treating well-differentiated thyroid cancers

2 weeks

Multiple visits for radiotherapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, with primary focus on safety as defined by the incidence of maximum grade 3 or greater NCI CTCAE toxicity

4 weeks

1-2 visits (in-person)

Efficacy Evaluation

Efficacy of the treatment is evaluated at 6 months using RECIST criteria, SPECT imaging, and changes in serum thyroglobulin levels

6 months

What Are the Treatments Tested in This Trial?

Interventions

• External Beam Radiotherapy (XRT)
• Radioactive Iodine (RAI)

Trial Overview The study tests combining external beam radiation (XRT) with radioactive iodine (RAI) treatment in patients with metastatic thyroid cancer. The aim is to safely deliver higher tumor radiation doses through precise dosimetric planning. Researchers will monitor safety based on severe toxicity incidence during and after treatment.

How Is the Trial Designed?

Group I: High-risk thyroid cancer patients Experimental Treatment 1 Intervention

All study patients will have histologically confirmed recurrence of thyroid cancer that is incompletely responsive to initial surgery.

External Beam Radiotherapy (XRT) is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as External Beam Radiotherapy for:

• Thyroid cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in United States as External Beam Radiotherapy for:

• Thyroid cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors
• Cervical cancer
• Esophageal cancer

Approved in Canada as External Beam Radiotherapy for:

• Thyroid cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in Japan as External Beam Radiotherapy for:

• Thyroid cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in China as External Beam Radiotherapy for:

• Thyroid cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in Switzerland as External Beam Radiotherapy for:

• Thyroid cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

External-beam radiation therapy (EBRT) can effectively improve local control in differentiated thyroid cancer, especially in patients with gross residual disease after surgery, as indicated by retrospective studies.

EBRT is particularly beneficial for patients over 45 years old with a high risk of relapse, as it can enhance the local relapse-free rate and is safe with acceptable acute toxicity and rare serious long-term complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External-beam radiation therapy in the treatment of differentiated thyroid cancer. Brierley, JD., Tsang, RW.[2019]

Patients with well-differentiated thyroid carcinoma who received external beam radiotherapy (XRT) reported significant declines in quality of life, particularly in chewing, swallowing, and appetite, as well as increased pain compared to those treated with total thyroidectomy (TT) or TT with radioactive iodine (RAI).

The study found that while both RAI and XRT negatively impacted quality of life compared to TT alone, XRT led to additional morbidity, highlighting the need for careful consideration of treatment options in managing advanced thyroid cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life impact of external beam radiotherapy for advanced thyroid carcinoma. Gal, TJ., Streeter, M., Burris, J., et al.[2019]

Radioactive iodine (RAI) therapy, used since 1946 to treat thyroid cancer, effectively ablates residual thyroid tissue and treats metastases, but it carries both acute and long-term risks.

Common acute side effects include nausea, loss of taste, and salivary gland swelling, while long-term complications can involve chronic mouth pain, dental issues, and an increased risk of second cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of radioactive iodine treatment of thyroid carcinoma. Lee, SL.[2019]

In a study of 36 patients with differentiated thyroid cancer, external-beam radiotherapy (EBRT) doses greater than 50 Gy significantly improved control rates of metastatic or recurrent lesions, achieving a 100% control rate for this dosage group.

Adding radioactive iodine therapy (RAIT) after EBRT resulted in a much higher two-year control rate of 89% compared to 45% for those who did not receive RAIT, indicating that this combination therapy can enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment intensity and control rates in combining external-beam radiotherapy and radioactive iodine therapy for metastatic or recurrent differentiated thyroid cancer. Makita, K., Hamamoto, Y., Tsuruoka, S., et al.[2020]

External beam radiotherapy (EBRT) is established as an effective adjuvant treatment for anaplastic thyroid cancer, especially when combined with taxanes, enhancing treatment outcomes.

Recent evidence supports the use of EBRT in high-risk differentiated thyroid cancer, aligning with recommendations from major thyroid associations, while advancements in radiation delivery techniques promise improved efficacy and reduced toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on external beam radiation therapy in thyroid cancer. Brierley, JD.[2011]

In a study of 49 patients with locally advanced iodine refractory-differentiated thyroid cancer, postoperative external beam radiotherapy (EBRT) significantly improved locoregional control (LRC) and overall survival (OS), especially in patients with microscopic residual disease (R1) compared to macroscopic residual disease (R2).

The 5-year LRC rate was 84.3% for R1 and 44.9% for R2, while the 5-year OS rate was 72.1% for R1 and 33.1% for R2, indicating that EBRT is effective and has manageable side effects, primarily limited to mild acute toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative external beam radiotherapy for locoregional control in iodine refractory differentiated thyroid cancer. Groen, AH., van Dijk, D., Sluiter, W., et al.[2022]

In a study of 41 patients treated with external beam radiotherapy (EBRT) for differentiated thyroid cancer, the most common reasons for treatment included macroscopic residual disease (56%) and microscopic residual disease (25%).

The study suggests a potential dose-response relationship, as patients receiving higher doses of EBRT (>54 Gy) had lower local recurrence rates (18% recurrence) compared to those receiving lower doses (<50 Gy with 63% recurrence), indicating that higher doses may improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiotherapy in the management of differentiated thyroid cancer. Ford, D., Giridharan, S., McConkey, C., et al.[2019]

A retrospective review of 1300 patients with papillary thyroid carcinoma (PTC) suggests that postoperative radioactive iodine (RAI) treatment is recommended for patients with pT2-pT4 and pN0-pN1b classifications, while external beam radiotherapy (EBRT) is advised for those with more aggressive features such as gross residual disease or positive margins.

The study highlights the potential benefits of EBRT in select high-risk patients with PTC, indicating that while there is variability in treatment recommendations across different centers, EBRT can add value to the management of PTC in specific cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of external beam radiotherapy in the treatment of papillary thyroid cancer. Lee, N., Tuttle, M.[2022]

In a study of 729 patients with differentiated thyroid cancer, radioactive iodine (RAI) treatment significantly improved the local-regional relapse-free rate (LRFR), but did not show a benefit for low-risk patients under 45 years old.

External beam radiotherapy (RT) provided a significant survival advantage for high-risk patients over 60 years old, improving both cause-specific survival (CSS) and LRFR compared to those who did not receive RT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic factors and the effect of treatment with radioactive iodine and external beam radiation on patients with differentiated thyroid cancer seen at a single institution over 40 years. Brierley, J., Tsang, R., Panzarella, T., et al.[2022]

Radioactive iodine (RAI) is an important adjuvant therapy for differentiated thyroid cancer, providing significant benefits when used in properly selected patients.

External beam radiation therapy (EBRT) enhances locoregional control and offers palliative effects for high-risk patients, although recommendations for both therapies are primarily based on retrospective studies due to the lack of prospective randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A risk-adapted approach to the use of radioactive iodine and external beam radiation in the treatment of well-differentiated thyroid cancer. Tuttle, RM., Rondeau, G., Lee, NY.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4975923/

External-beam radiotherapy for differentiated thyroid cancer ... In general, the use of intensity-modulated radiotherapy (IMRT) with doses >60 Gy results in higher likelihood of long-term control. Many retrospective studies ...

2. redjournal.org redjournal.org/article/S0360-3016(25)06313-8/fulltext

The role of external beam radiation therapy in thyroid ... Patients treated with curative-intent EBRT had significantly better 1-year survival (42.9% vs. 14.3%, p = 0.0001), highlighting the prognostic ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625063138

The role of external beam radiation therapy in thyroid ... In DTC, poRT combined with radioactive iodine (RAI) reduced the 5-year locoregional recurrence rate by up to 30% in high-risk patients ( ...

4. oncodaily.com oncodaily.com/oncolibrary/radiotherapy/radiotherapy-for-thyroid-cancer

Radiotherapy For Thyroid Cancer: Types, Success Rate, ... With a median follow-up of 33.7 months, the results showed high efficacy and safety: all patients maintained locoregional control, and the 2- ...

5. mdpi.com mdpi.com/2673-592X/1/3/16

Treatment Outcomes of External Beam Radiation Therapy ... In conclusion, EBRT achieved tumor size reduction in 73% of patients, among whom 75% had tumor size reduction within 6 months of EBRT completion ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2331518024000556

Outcomes and Toxicities of Nonmedullary Thyroid Tumors ... Altogether, our findings demonstrate that proton beam radiation is both safe and feasible in the management of patients with thyroid cancer, including those ...