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

Phase 3

Active, not recruiting

• Conditions: Medullary Thyroid Cancer
• Interventions: Drug: Selpercatinib; Drug: Cabozantinib; Drug: Vandetanib

• Registration Number: NCT04211337
• Lead Sponsor: Loxo Oncology, Inc.

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.

Study Timeline

• Study First Submitted: 2019-12-24
• Study First Submitted QC: 2019-12-24
• Study First Posted: 2019-12-26
• Study Start: 2020-02-11
• Primary Completion: 2023-05-22
• Results First Submitted: 2024-03-12
• Results First Submitted QC: 2024-05-20
• Results First Posted: 2024-06-13
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-20
• Study Completion: 2026-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 291

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cabozantinib or Vandetanib - Treatment B (TRT B)	Vandetanib	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
Selpercatinib - Treatment A (TRT A)	Selpercatinib	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).
Cabozantinib or Vandetanib - Treatment B (TRT B)	Cabozantinib	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

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)	Baseline to Progressive Disease or Death from Any Cause, Whichever Occurs First, Up to 39 Months	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.

Secondary Outcome Measures

Name	Time	Method
Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)	Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months	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).
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR	Baseline through Disease Progression or Death Up to 39 Months	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.
Duration of Response (DoR) by BICR	Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 39 Months	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.
Overall Survival (OS)	Baseline	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.
PFS2 by Investigator	Baseline	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.
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)	Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months	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.
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)	Baseline

Trial Locations

Locations (141)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

UCLA Hematology/Oncology - Westwood (Building 100); 🇺🇸 Los Angeles, California, United States

University of California Davis (UC Davis) Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center; 🇺🇸 Torrance, California, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

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