A study to evaluate the efficacy and safety of pralsetinib compared with SOC treatment (cabozantinib or vandetanib) for participants with RET (rearranged during transfection)-mutant MTC who have not previously received a SOC MultiKinase Inhibitor (MKI) therapy. Participants will be randomized in a 1:1 ratio into one of two treatment arms: Arm A (pralsetinib) or Arm B (investigator's choice of either cabozantinib or vandetanib for adults and vandetanib for adolescents). Participants whose disease progresses during SOC treatment will be offered the option to cross over to receive pralsetinib after confirmation of progressive disease by blinded independent central review (BICR).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Participants will receive pralsetinib at a dose of 400 mg, as per the dosing schedule described above.
Adult participants will receive cabozantinib at a dose of 140 mg, as per the dosing schedule described above.
Adult participants will receive vandetanib at a dose of 300 mg and adolescent participants will receive vandetanib as per the dosing schedule described above.
Hospital Universitario Virgen del Rocio
Seville, Spain
Progression-Free Survival (PFS)
Defined as the time from randomization date to the first documented PD (Progression of Disease), as assessed by BICR according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) or death due to any cause, whichever occurs first.
Time frame: Up to 5 years
Time-To-Treatment Failure (TTF)
Defined as the time from randomization date to the discontinuation of study drug during the treatment period due to death, treatment-related adverse event, or PD, as assessed by BICR according to RECIST v1.1, whichever occurs first.
Time frame: Up to 13 years
Objective Response Rate (ORR)
Defined as the proportion of participants who achieve a CR (Complete Response) or a PR (Partial Response) prior to progressive disease and/or other anti-cancer therapy, as assessed by BICR according to RECIST v1.1.
Time frame: Up to 13 years
Overall Survival (OS)
Defined as the time from randomization date to death due to any cause.
Time frame: Up to 13 years
Percentage of Participants With Adverse Events (AEs)
Incidence and severity determined according to the NCI CTCAE v5.0 (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0) criteria.
Time frame: Up to 13 years
Duration of Response (DOR)
Defined as the number of weeks from the time criteria are first met for either a CR or a PR, until the date of documented PD, as assessed by BICR according to RECIST v1.1, or death due to any cause, whichever occurs first.
Time frame: Up to 13 years
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Disease Control Rate (DCR)
Defined as the proportion of participants who experience a best response of CR, PR, or stable disease, as assessed by BICR according to RECIST v1.1.
Time frame: Up to 13 years
Clinical Benefit Rate (CBR)
Defined as the proportion of participants who experience a CR or a PR or a best response of stable disease with a minimum duration of 6 months, as assessed by BICR according to RECIST v1.1.
Time frame: Up to 13 years
Time to Deterioration of Function
Defined as the time from randomization to the date of a participant's first \>= 10-point decrease from baseline score, as assessed through the use of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).
Time frame: Up to 13 years
Quality of Life (QoL)
Defined as the time from randomization to the date of a participant's first \>= 10-point decrease from baseline score, as assessed through the use of the GHS (Global Health Status)/QoL scales.
Time frame: Up to 13 years
Acceptability and Palatability of Pralsetinib Capsules
Acceptability Survey scores on Day 1 of Cycle 1 and Crossover Cycle 1 (each cycle is 28 days).
Time frame: Up to 13 years