Selpercatinib + I-131 for Thyroid Cancer

Recruiting at 5 trial locations

Overseen By Lori J. Wirth, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Investigational agents, QTc prolongation drugs

Disqualifiers: Symptomatic CNS metastasis, Cardiovascular disease, Uncontrolled hypertension, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-8 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is being done to determine the efficacy of selpercatinib to restore radioactive iodine (I-131 NaI) uptake and allow for I-131 treatment in people with RET fusion-positive radioiodine-refractory thyroid cancer. This research study involves the study drug selpercatinib in combination with standard of care treatments, I-131 and thyrotropin alfa (rhTSH).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking medications that cause QTc prolongation (a heart rhythm condition) or if you have had certain treatments like chemotherapy or radiotherapy within the last 4 weeks.

What data supports the effectiveness of the drug Selpercatinib for thyroid cancer?

Selpercatinib has been shown to be effective in treating advanced RET-altered thyroid cancer, with a high overall response rate in clinical trials. It was approved by the FDA based on significant responses in patients with RET fusion-positive thyroid cancer, demonstrating prolonged durations of response. ^{1 2 3 4 5}

Is the combination of Selpercatinib and I-131 safe for humans?

Selpercatinib has been shown to have an acceptable safety profile in clinical trials for lung and thyroid cancers, with common side effects including high blood pressure and liver enzyme changes. Most side effects were manageable with dose adjustments, and only a few patients stopped treatment due to these effects. The product label warns about potential risks like liver damage, high blood pressure, heart rhythm changes, bleeding, allergic reactions, and risks to unborn babies. ^{1 3 5 6 7}

What makes the drug Selpercatinib unique for thyroid cancer treatment?

Selpercatinib is unique because it specifically targets RET gene alterations, which are changes in a gene that can drive cancer growth. This drug is particularly effective for patients whose thyroid cancer is resistant to radioactive iodine, offering a new option for those with limited treatment choices. ^{1 2 3 6 8}

Research Team

Lori J Wirth, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Adults and children (12+) with certain types of advanced thyroid cancer that have a specific gene change called RET fusion. They must be able to swallow pills, not have had recent major treatments or surgeries, and should not be pregnant or breastfeeding. People with controlled HIV or hepatitis are eligible, but those with serious heart conditions, uncontrolled infections, or other severe illnesses cannot join.

Inclusion Criteria

WOCBP must have a negative pregnancy test (serum or urine) within 24 hours prior to initiating study treatment, and not be breast-feeding during treatment and for ≥1 week after the last dose of study therapy

I am between 12 and 18 years old with a visible tumor.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I have high or low calcium levels causing symptoms.

I do not have brain metastases causing symptoms or at risk of spinal cord compression.

I am taking medication that can affect my heart's rhythm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selpercatinib for 4 weeks, with a therapeutic dose of I-131 NaI administered in the fourth week. A second 4-week course may be offered if radioiodine uptake is restored.

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits for up to 2 years.

2 years

Treatment Details

Interventions

• rhTSH
• Selpercatinib
• Sodium Iodine I-131

Trial Overview The trial is testing if the drug selpercatinib can make thyroid cancers that no longer respond to radioactive iodine treatment start responding again. Participants will receive selpercatinib along with standard treatments including I-131 and rhTSH injections.

Participant Groups

Group I: SELPERCATINIB + I-131 NaI Experimental Treatment 3 Interventions

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Participants will be treated with Selpercatinib for 4 weeks. * In the fourth week of treatment, participants will receive a therapeutic dose of I-131 NaI. * Those participants in whom radioiodine uptake has been restored may be offered a second 4-week course of selpercatinib plus I-131 NaI treatment

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

Approved in United States as RETEVMO for:

• RET fusion-positive or RET mutant thyroid cancers
• non-small cell lung cancer
• advanced or metastatic medullary thyroid cancer
• advanced or metastatic thyroid cancer with RET gene fusion
• locally advanced or metastatic solid tumors with RET gene fusion

Approved in European Union as RETEVMO for:

• RET-driven non-small cell lung cancer
• medullary thyroid cancer
• thyroid cancer

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Selpercatinib (RETEVMO™) is a targeted therapy that inhibits the RET receptor tyrosine kinase, specifically designed for cancers with RET alterations.

It received FDA approval based on the promising results from the phase I/II LIBRETTO-001 trial for treating RET fusion-positive non-small-cell lung cancer, RET fusion-positive thyroid cancer, and RET-mutant medullary thyroid cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib: First Approval. Markham, A.[2021]

In a phase II study involving 77 Chinese patients with advanced RET-altered thyroid cancer, selpercatinib demonstrated a high objective response rate (ORR) of 57.7% in the primary analysis set, indicating its efficacy in this population.

The treatment was generally well tolerated, with 59.7% of patients experiencing grade 3 or higher adverse events, leading to dose reductions in 32.5% of cases, suggesting that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of selpercatinib in Chinese patients with advanced RET-altered thyroid cancers: results from the phase II LIBRETTO-321 study. Zheng, X., Ji, Q., Sun, Y., et al.[2022]

Selpercatinib received accelerated FDA approval for treating specific cancers associated with RET alterations, showing overall response rates (ORR) of 64% in RET fusion-positive non-small cell lung cancer and 100% in RET fusion-positive thyroid cancer, based on a multicenter clinical trial with significant duration of responses.

While effective, selpercatinib has safety warnings for potential side effects such as hepatotoxicity, hypertension, and embryo-fetal toxicity, highlighting the importance of monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Selpercatinib for the Treatment of Lung and Thyroid Cancers with RET Gene Mutations or Fusions. Bradford, D., Larkins, E., Mushti, SL., et al.[2022]

Selumetinib, a targeted multikinase inhibitor, has shown limited effectiveness as a single-agent treatment for patients with papillary thyroid carcinoma that have the (V600E)BRAF mutation.

This study highlights the focus on targeting the mitogen-activated protein kinase pathway, which is crucial for understanding treatment options for patients with progressive radioactive iodine-refractory thyroid cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In search of a real "targeted" therapy for thyroid cancer. Brose, MS.[2019]

Selpercatinib, a novel specific RET inhibitor approved by the FDA in May 2020, targets RET alterations in lung and thyroid cancers, offering a more effective treatment option compared to multi-kinase inhibitors that often cause off-target toxicity.

The review discusses selpercatinib's mechanism of action and clinical data, highlighting its potential to improve outcomes for patients with RET-altered malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib for lung and thyroid cancers with RET gene mutations or fusions. Zheng, H., Chen, ZS., Li, J.[2021]

Selpercatinib is an effective oral treatment for advanced RET fusion-positive non-small cell lung cancer (NSCLC), showing strong and lasting responses in both previously treated and treatment-naïve patients during a pivotal phase 1/2 clinical trial.

The drug has a manageable safety profile, with most adverse events being manageable through dose adjustments, and only a small number of patients discontinuing treatment due to side effects, which primarily included hypertension and elevated liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib: A Review in Advanced RET Fusion-Positive NSCLC. Nie, T., Syed, YY.[2023]

Selpercatinib, a selective RET inhibitor, can cause significant thyroid dysfunction, leading to clinical hypothyroidism in athyreotic patients with RET-mutant medullary thyroid carcinoma, despite adequate levothyroxine supplementation.

The mechanism behind this thyroid dysfunction appears to be an off-target effect of selpercatinib that inhibits D2-mediated T3 production, necessitating liothyronine supplementation to restore normal T3 levels in affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selpercatinib-Induced Hypothyroidism Through Off-Target Inhibition of Type 2 Iodothyronine Deiodinase. Boucai, L., Salas-Lucia, F., Krishnamoorthy, GP., et al.[2023]

A 13-year-old girl with metastatic papillary thyroid carcinoma (PTC) that was resistant to radioactive iodine showed significant improvement after treatment with the RET inhibitor selpercatinib, including reduced need for supplemental oxygen and decreased tumor size.

The patient's positive response to selpercatinib, despite dose reductions due to weight gain, highlights the potential efficacy of targeted therapies for RET gene rearrangements in pediatric PTC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained Response with Dose-reduced Selpercatinib in a Pediatric Patient with Metastatic NCOA4-RET Fusion Papillary Thyroid Carcinoma. Suydam, AC., Bach, A., Markovina, S., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Selpercatinib: First Approval. [2021]

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

Efficacy and safety of selpercatinib in Chinese patients with advanced RET-altered thyroid cancers: results from the phase II LIBRETTO-321 study. [2022]

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

FDA Approval Summary: Selpercatinib for the Treatment of Lung and Thyroid Cancers with RET Gene Mutations or Fusions. [2022]

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

In search of a real "targeted" therapy for thyroid cancer. [2019]

5. Spain pubmed.ncbi.nlm.nih.gov

Selpercatinib for lung and thyroid cancers with RET gene mutations or fusions. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Selpercatinib: A Review in Advanced RET Fusion-Positive NSCLC. [2023]

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

Selpercatinib-Induced Hypothyroidism Through Off-Target Inhibition of Type 2 Iodothyronine Deiodinase. [2023]

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

Sustained Response with Dose-reduced Selpercatinib in a Pediatric Patient with Metastatic NCOA4-RET Fusion Papillary Thyroid Carcinoma. [2023]