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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
291
Administered orally
Administered orally
Administered orally
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
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.
Time frame: Baseline to Progressive Disease or Death from Any Cause, Whichever Occurs First, Up to 39 Months
Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)
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).
Time frame: Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR
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.
Time frame: Baseline through Disease Progression or Death Up to 39 Months
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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
...and 133 more locations
Duration of Response (DoR) by BICR
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.
Time frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 39 Months
Overall Survival (OS)
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.
Time frame: Baseline
PFS2 by Investigator
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.
Time frame: Baseline
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)
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.
Time frame: Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months
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