NCT04211337 · CITED IN SOURCE DOCUMENTS

A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-03-19

The reason for this study is to see if the study drug selpercatinib is safe and more effective compared to a standard treatment in participants with rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)

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outcome · POSTED

Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)

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outcome · POSTED

Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR

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outcome · POSTED

Duration of Response (DoR) by BICR

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outcome · NOT POSTED

Overall Survival (OS)

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outcome · NOT POSTED

PFS2 by Investigator

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outcome · POSTED

Comparative Tolerability: Number of Weeks With High Side Effect Bother Based Score of 3 or 4 on the Functional Assessment of Cancer Therapy Item GP5 (FACT-GP5)

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outcome · NOT POSTED

The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants With RET-Positive Specimens as Called by the Central Lab, Which is Also RET-Positive as Called by a Local Lab (Positive Percent Agreement)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: * At least 18 years of age (participants as young as 12 years of age will be allowed if permitted by local regulatory authorities). * Histologically or cytologically confirmed, unresectable, locally advanced and/or metastatic MTC and no prior history of treatment with kinase inhibitors for advanced/metastatic disease. * Radiographic progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at screening compared with a previous image taken within the prior 14 months as assessed by the BICR. Participants with measurable or non-measurable but evaluable disease are eligible; however, participants with non-measurable disease may not have disease limited to bone sites only. * A defined/acceptable RET gene alteration identified in a tumor, germline deoxyribonucleic acid (DNA) or blood sample. * Tumor tissue in sufficient quantity to allow for retrospective central analysis of RET mutation status * Eastern Cooperative Oncology Group performance status score of 0 to 2. * Adequate hematologic, hepatic, and renal function and electrolytes. * Men and women of childbearing potential must agree to use a highly effective contraceptive method during treatment with study drug and for 4 months following the last dose of study drug. * Ability to swallow capsules. Exclusion Criteria: * An additional validated oncogenic driver in MTC if known that could cause resistance to selpercatinib treatment. Examples include, but are not limited to RAS or BRAF gene mutations and NTRK gene fusions. * Symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. * Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months, history of Torsades de pointes, or prolongation of the QTcF \>470 milliseconds on more than one electrocardiogram (ECG) during screening. Participants who are intended to receive vandetanib if randomized to the control arm are ineligible if QTcF is \>450 milliseconds. * Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing uncontrolled intercurrent illness. * Active hemorrhage or at significant risk for hemorrhage. * Other malignancy unless nonmelanoma skin cancer, carcinoma in situ or malignancy diagnosed ≥2 years previously and not currently active. Participants with multiple endocrine neoplasia type 2 (MEN2) associated pheochromocytoma may be eligible.
healthy Volunteers: false
minimum Age: 12 Years
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
160 milligrams Selpercatinib administered orally (PO) twice daily (BID). Adolescent Dose: 92 milligrams per square meter (mg/m2) BID (not to exceed 160 mg BID).
intervention Names
Drug: Selpercatinib
label
Selpercatinib - Treatment A (TRT A)
type
EXPERIMENTAL
description
140 mg Cabozantinib administered orally daily (QD) or 300 mg Vandetanib administered orally QD per physician choice. Cabozantinib Adolescent Dose: 40 mg/m2. Vandetanib Adolescent Dose: * 0.7 - \<0.9 - 100 mg every other day (QOD) * 0.9 - \<1.2 - 100 mg QD * 1.2 - \<1.6 - 7-day schedule 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - 200 mg - 100 mg * ≥1.6 - 200 QD
intervention Names
Drug: Cabozantinib
Drug: Vandetanib
label
Cabozantinib or Vandetanib - Treatment B (TRT B)
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Selpercatinib - Treatment A (TRT A)
description
Administered orally
name
Selpercatinib
other Names
LY3527723
LOXO-292
type
DRUG
arm Group Labels
Cabozantinib or Vandetanib - Treatment B (TRT B)
description
Administered orally
name
Cabozantinib
type
DRUG
arm Group Labels
Cabozantinib or Vandetanib - Treatment B (TRT B)
description
Administered orally
name
Vandetanib
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 291
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria, or death from any cause in the absence of BICR-documented progressive disease. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
measure
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
time Frame
Baseline to Progressive Disease or Death from Any Cause, Whichever Occurs First, Up to 39 Months

secondary Outcomes

description
TFFS by BICR is defined as the time from randomization to the first occurrence of: * documented radiographic disease progression per RECIST 1.1 as assessed by BICR; or * unacceptable toxicity leading to treatment discontinuation as assessed by the investigator. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. To qualify as an event, the toxicity must be from an intolerable AE (defined as any study drug-related AE that meets protocol guidance for treatment discontinuation, with the exception of alopecia); or death (due to any cause).
measure
Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)
time Frame
Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months
description
ORR is defined as the number of participants who achieved the best overall response (BOR) of CR or PR divided by the total number of participants randomized to each treatment arm. ORR per RECIST 1.1 as assessed by BICR.
measure
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR
time Frame
Baseline through Disease Progression or Death Up to 39 Months
description
DoR by BICR is defined as the time from the date that measurement criteria for complete response (CR) or partial response (PR) (whichever is first recorded) are first met by the BICR or investigator assessment, as applicable, until the first date that disease is recurrent or documented disease progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of documented disease progression or recurrence. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
measure
Duration of Response (DoR) by BICR
time Frame
Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 39 Months
description
Overall survival (OS) is defined as the time from randomization until death from any cause. If the participant is alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the participant is known to be alive.
measure
Overall Survival (OS)
time Frame
Baseline
description
Progression-free survival 2 (PFS2) is defined as the time from randomization to disease progression (radiographic or symptomatic progression as determined by the investigator) on the next line of treatment or death from any cause in the absence of observed disease progression. If the participant is alive at the cutoff for analysis, and disease progression has not been observed, PFS2 data will be censored on the latest date of last progression-free assessment or start of the next line of treatment.
measure
PFS2 by Investigator
time Frame
Baseline
description
Comparative tolerability defined as a comparison of the proportion of time on treatment with high side effect bother as assessed by the FACT-GP5. The FACT-GP5 is a single question used to assess the overall bother of the treatment side effects. It is scored using a 5-point rating scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; and 4 = very much), where lower scores reflect less bother from treatment side effects. Time with high side effect bother (i.e.) score of 3 or 4 is reported here and was derived as follows: cumulative amount of time, in weeks, during which a participant reports high side effect bother divided by the total duration of therapy (weeks), derived as (date of last study treatment dose - date of first study treatment dose + 1) divided by 7.
measure
Comparative Tolerability: Number of Weeks With High Side Effect Bother Based Score of 3 or 4 on the Functional Assessment of Cancer Therapy Item GP5 (FACT-GP5)
time Frame
Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months
measure
The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants With RET-Positive Specimens as Called by the Central Lab, Which is Also RET-Positive as Called by a Local Lab (Positive Percent Agreement)
time Frame
Baseline

Full study description

brief Summary: The reason for this study is to see if the study drug selpercatinib is safe and more effective compared to a standard treatment in participants with rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.
detailed Description: Adaptive sample size re-estimation will be performed at interim analysis. The sample size could be increased from approximately 250 to 400 depending on the results of interim analysis.

Source references

references

citation
Payakachat N, Gilligan AM, Altman D, Maeda P, Choi J, Bourke S, Speck RM, Spies E, Kopeckova K, Elisei R, Wadsley J, Krajewska J. Assessing side-effect bother, burden, and tolerability: A qualitative study exploring the content validity of the Functional Assessment of Cancer Therapy - Item GP5. J Geriatr Oncol. 2025 Sep;16(7):102304. doi: 10.1016/j.jgo.2025.102304. Epub 2025 Jul 4.
pmid
40617171
type
DERIVED
citation
Regnault A, Bunod L, Loubert A, Brose MS, Hess LM, Maeda P, Lin Y, Speck RM, Gilligan AM, Payakachat N. Assessing tolerability with the Functional Assessment of Cancer Therapy item GP5: psychometric evidence from LIBRETTO-531, a phase 3 trial of selpercatinib in medullary thyroid cancer. J Patient Rep Outcomes. 2024 Dec 19;8(1):149. doi: 10.1186/s41687-024-00823-8.
pmid
39694978
type
DERIVED
citation
Hadoux J, Elisei R, Brose MS, Hoff AO, Robinson BG, Gao M, Jarzab B, Isaev P, Kopeckova K, Wadsley J, Fuhrer D, Keam B, Bardet S, Sherman EJ, Tahara M, Hu MI, Singh R, Lin Y, Soldatenkova V, Wright J, Lin B, Maeda P, Capdevila J, Wirth LJ; LIBRETTO-531 Trial Investigators. Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. N Engl J Med. 2023 Nov 16;389(20):1851-1861. doi: 10.1056/NEJMoa2309719. Epub 2023 Oct 21.
pmid
37870969
type
DERIVED
citation
Wirth LJ, Brose MS, Elisei R, Capdevila J, Hoff AO, Hu MI, Tahara M, Robinson B, Gao M, Xia M, Maeda P, Sherman E. LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naive RET-mutant medullary thyroid cancer. Future Oncol. 2022 Sep;18(28):3143-3150. doi: 10.2217/fon-2022-0657. Epub 2022 Aug 15.
pmid
35969032
type
DERIVED
citation
Jaber T, Dadu R, Hu MI. Medullary thyroid carcinoma. Curr Opin Endocrinol Diabetes Obes. 2021 Oct 1;28(5):540-546. doi: 10.1097/MED.0000000000000662.
pmid
34292174
type
DERIVED