Selpercatinib Before Surgery for Thyroid Cancer

Recruiting at 2 trial locations

Overseen By Mark Zafereo

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Selective RET inhibitors

Disqualifiers: Active cardiovascular disease, uncontrolled infections, 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: 28 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take any investigational anti-cancer therapy or medications that cause QTc prolongation while participating in the trial.

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, as demonstrated in clinical trials like LIBRETTO-001 and LIBRETTO-321. It is specifically approved for RET fusion-positive thyroid cancer and RET-mutant medullary thyroid cancer, indicating its targeted action against these cancer types. ^{1 2 3 4 5}

Is selpercatinib safe for humans?

Selpercatinib has been shown to have an acceptable safety profile in clinical trials for various cancers, with common side effects including high blood pressure, liver enzyme changes, and fatigue. Most side effects can be managed with dose adjustments, and only a small number of patients stopped treatment due to side effects. ^{1 2 6 7 8}

How is the drug selpercatinib unique for treating thyroid cancer?

Selpercatinib is unique because it specifically targets RET gene alterations, which are changes in the DNA that can drive cancer growth, making it effective for RET fusion-positive thyroid cancer. It is a first-in-class drug, meaning it's the first of its kind to be approved for this specific genetic target in thyroid cancer. ^{1 2 3 9 10}

What is the purpose of this trial?

This phase II trial studies the effect of selpercatinib given before surgery in treating patients with thyroid cancer whose tumors have RET alterations (changes in the genetic material \[deoxyribonucleic acid (DNA)\]). Selpercatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving selpercatinib before surgery may help shrink the tumors and help control the disease.

Research Team

Mark Zafereo

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with thyroid cancer showing RET gene changes, aged 12 or older, who can handle outpatient treatment and surgery. They must have a measurable tumor lesion and not have been treated with certain other RET inhibitors. Patients should be able to take contraceptives if of childbearing potential.

Inclusion Criteria

I can care for myself and remain up and about more than half of my waking hours.

Your hemoglobin level is at least 9 grams per deciliter.

Your platelet count is at least 100,000 per microliter.

Exclusion Criteria

I have uncontrolled high or low calcium levels causing symptoms.

You had a very strong allergic reaction (grade 3 or higher) to selpercatinib or any of its ingredients.

I do not have any uncontrolled infections or serious illnesses like high blood pressure or diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selpercatinib orally twice daily for 28-day cycles, repeated up to 7 cycles

28 weeks

Monthly visits for each cycle

Surgery

Participants undergo standard of care surgery after completion of selpercatinib treatment

Follow-up

Participants are monitored for disease progression status every 3-4 months for the first 2 years, and every 6 months for years 3 and 4, then once in year 5

5 years

Treatment Details

Interventions

• Selpercatinib
• Therapeutic Conventional Surgery

Trial Overview The study tests the effects of Selpercatinib given before surgery on thyroid cancer patients with genetic alterations in the RET gene. The goal is to see if it can shrink tumors and control disease progression prior to surgical intervention.

Participant Groups

Group I: Treatment (selpercatinib) Experimental Treatment 4 Interventions

Patients receive selpercatinb PO BID on days 1-28. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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 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, 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 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 (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]

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]

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]

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. England 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. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

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

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

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. [2023]

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

FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors. [2023]

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

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

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Structural basis of acquired resistance to selpercatinib and pralsetinib mediated by non-gatekeeper RET mutations. [2021]