Selpercatinib for Thyroid Cancer

(RAISE Trial)

Recruiting at 1 trial location

Overseen By Meghan Donnelly, MPH

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital of Philadelphia

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors, QTc prolongers

Disqualifiers: Pregnancy, Cardiovascular disease, 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

13 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called selpercatinib for individuals with papillary thyroid cancer that has spread to the lungs. The researchers aim to determine if selpercatinib, followed by radioactive iodine therapy, can benefit patients who have not responded well to traditional treatments. Suitable candidates for this trial have a specific type of thyroid cancer with lung nodules visible on a CT scan and a genetic change in their cancer known as a RET alteration. This trial provides an opportunity to explore an alternative treatment approach that could potentially improve outcomes. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants, allowing them to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take strong CYP3A4 inducers or inhibitors starting 14 days before the trial and during the study. Also, you should avoid medications that cause QTc prolongation.

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

Research shows that selpercatinib is usually well-tolerated by patients. Long-term safety data from studies indicates that this treatment provides lasting benefits for people with thyroid cancer. Most side effects are manageable and include dry mouth, diarrhea, and changes in liver function, so regular liver function checks are necessary. Serious side effects are less common but can occur. Patients in trials must be closely monitored by medical professionals to address any issues promptly. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for thyroid cancer?

Researchers are excited about selpercatinib for thyroid cancer because it targets a specific genetic mutation, RET, which plays a key role in the growth of certain thyroid cancers. Unlike traditional treatments such as surgery, radioactive iodine (RAI), and external beam radiation, which are more general approaches, selpercatinib is a targeted therapy designed to inhibit the RET kinase. This precision makes selpercatinib potentially more effective for patients with RET-positive thyroid cancer, offering a more personalized and potentially less toxic treatment option. Additionally, combining selpercatinib with 131I therapy might enhance the effectiveness of the radioactive iodine, providing a novel approach to treating advanced cases.

What evidence suggests that selpercatinib might be an effective treatment for papillary thyroid cancer?

Studies have shown that selpercatinib effectively treats certain types of thyroid cancer. In earlier research, 73% of patients with RET-mutant medullary thyroid cancer responded well to selpercatinib. Another study found that selpercatinib helped patients live longer without cancer progression compared to treatments like cabozantinib or vandetanib. This treatment targets specific changes in cancer cells, helping to control the disease and extend survival. In this trial, participants will receive selpercatinib monotherapy followed by 131I therapy. These findings suggest selpercatinib could be a promising treatment for papillary thyroid cancer, especially for patients who do not respond well to current options. ^{2 3 5 6 7}

Who Is on the Research Team?

Theodore W. Laetsch

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for young patients aged 2-21 with advanced differentiated thyroid cancer post-surgery, who have multiple lung nodules or enlarging ones consistent with metastatic disease. They must have a RET gene alteration and good organ function, including blood counts and liver/kidney performance.

Inclusion Criteria

Agreement to use contraception during treatment

Negative pregnancy test for women of childbearing potential documented within 24 hours prior to treatment

I am between 2 and 21 years old.

Exclusion Criteria

I have not had any systemic treatment for thyroid cancer.

I am not pregnant or breastfeeding.

I am not taking any strong drugs that affect liver enzyme activity.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Selpercatinib Treatment

Participants receive selpercatinib monotherapy for 6 months at the FDA-approved dose

6 months

131I Therapy

Participants receive 131I therapy after 6 months of selpercatinib treatment

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• 131I Therapy
• Selpercatinib

Trial Overview The study tests Selpercatinib monotherapy before traditional radioactive iodine (RAI) therapy in pediatric thyroid cancer patients. It aims to see if pre-treatment with Selpercatinib can improve responses to RAI, which has limited effectiveness on its own.

How Is the Trial Designed?

Group I: Experimental: Selpercatinib Monotherapy with 131I Therapy Experimental Treatment 2 Interventions

Patients will receive selpercatinib monotherapy for 6 months at the FDA-approved dose. Patients will receive 131I therapy after 6 months of selpercatinib. Selpercatinib will be continued for 5 days after RAI therapy and then patients will enter a wait and see period off treatment. Patients who experience disease progression at any point while on selpercatinib will proceed to 131I therapy and discontinue selpercatinib.

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?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

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

Published Research Related to This Trial

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 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]

In a phase 3 trial with 291 patients, selpercatinib demonstrated significantly better progression-free survival compared to cabozantinib or vandetanib, with a hazard ratio of 0.28, indicating a 72% reduction in the risk of disease progression or death.

Selpercatinib also showed a higher overall response rate of 69.4% compared to 38.8% in the control group, and it resulted in fewer treatment-related adverse events leading to dose reductions or discontinuations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. Hadoux, J., Elisei, R., Brose, MS., et al.[2023]

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]

Selpercatinib demonstrated a clinically meaningful objective response rate of 43.9% in patients with RET fusion-positive advanced solid tumors, indicating its efficacy in a diverse, tumor-agnostic population of 45 patients enrolled in the LIBRETTO-001 trial.

The safety profile of selpercatinib was consistent with previous studies, with common grade 3 or worse adverse events including hypertension and liver enzyme increases, but no treatment-related deaths were reported, highlighting its relative safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. Subbiah, V., Wolf, J., Konda, B., et al.[2022]

Selpercatinib (Retevmo) received accelerated FDA approval for treating adult patients with advanced solid tumors that have RET gene fusions, showing a 44% overall response rate in a study of 41 patients with various tumor types.

The treatment demonstrated a median duration of response of 24.5 months, indicating its potential long-term efficacy, while common side effects included edema, diarrhea, and fatigue, affecting over 25% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors. Duke, ES., Bradford, D., Marcovitz, M., et al.[2023]

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 (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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10777663/

Efficacy of Selpercatinib in RET-Altered Thyroid Cancers - PMC In 88 patients with RET-mutant vandetanib and cabozantinib-naïve medullary thyroid cancer, the response rate was 73% (95% CI, 62–82) and 1-year ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02503

Activated Thyroid Cancer: Long-Term Safety and Efficacy ... Three-year OS rates among patients in the treatment-naïve and pretreated groups were 94.4% and 65.5%, respectively. Safety. Treatment-emergent ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11592841/

Real-World Outcomes of Selective RET Inhibitor ... The phase 3 LIBRETTO-531 trial (NCT04211337) further established selpercatinib's efficacy in first-line treatment, showing superior PFS compared ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2309719

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant ... Selpercatinib treatment resulted in superior progression-free survival and treatment failure–free survival as compared with cabozantinib or vandetanib in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024077120

Efficacy and safety of selpercatinib in treating RET-altered ... Selpercatinib effectively controls the progression of thyroid cancer and prolongs patient survival through precise targeting, thereby providing ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39094065/

Long-Term Safety and Efficacy From LIBRETTO-001 - PubMed Three-year PFS rates were 75.2% and 87.3% among patients with cabozantinib/vandetanib-naïve MTC and treatment-naïve TC, respectively. Median PFS ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)01922-1/fulltext

2229P Updated safety and efficacy of selpercatinib in ... Conclusions. With longer f/u and additional pts, selpercatinib continues to demonstrate very durable responses in pts with RET-fusion thyroid cancer with or ...