Advanced RET-Altered Solid or Primary Central Nervous System Tumors
Conditions
Interventions
investigational material(s)
Generic name etc : Selpercatinib
INN of investigational material : Selpercatinib
Therapeutic category code : 429 Other antitumor agents
control material(s)
Generic name et
Sponsors
Eli Lilly and Company / ICCC :Medpace Japan KK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Advanced or metastatic solid or primary CNS tumor which has failed standard of care therapies -Evidence of an activating RET gene alteration in the tumor and/ or blood -Measurable or non-measurable disease -Karnofsky (participants 16 years and older) or Lansky (participants younger than 16) performance score of at least 50. -Participant with primary CNS tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days. -Adequate hematologic, hepatic and renal function. -Ability to receive study drug therapy orally or via gastric access -Willingness of men and women of reproductive potential to observe conventional and effective birth control
Exclusion criteria
Exclusion criteria: -Major surgery within two weeks prior to planned start of LOXO-292. -Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292. -Active uncontrolled systemic bacterial, viral, fungal or parasitic infection. -Clinically significant active malabsorption syndrome. -Pregnancy or lactation -Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant required a modification to current thyroid medication in the 7 days before start of LOXO-292). -Uncontrolled symptomatic hypercalcemia or hypocalcemia. -Known hypersensitivity to any of the components of the investigational agent, LOXO-292 or Ora-Sweet SF and OraPlus, for participants who will receive LOXO-292 suspension. -Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s]).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety For Phase 1 [ Time Frame: During the first 28-day cycle of LOXO-292 treatment ] -To determine the safety of oral LOXO-292 in pediatric participants with advanced solid tumors: Dose limiting toxicities (DLTs) -To determine the safety of oral LOXO-292 in pediatric participants with primary central nervous system (CNS) tumors: Dose limiting toxicities (DLTs) For Phase 2 [ Time Frame: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months) ] -Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Independent Review Committee (IRC) -ORR Based on Response Assessment in Neuro-Oncology (RANO) per IRC | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy pharmacokinetics other Phase 1 & Phase 2 [ Time Frame: Days 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days) ] -Area Under the Concentration-Time Curve from 0 to 24 hours (AUC0-24) of LOXO-292 -Maximum Concentration (Cmax) of LOXO-292 -Time to Maximum Concentration (Tmax) of LOXO-292 Phase 1 [ Time Frame: Days 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days) ] -Plasma Concentrations of LOXO-292 [ Time Frame: Cycle 1 (28 days) ] -Recommended LOXO-292 Dose for Phase 2 (MTD) [ Time Frame: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months) ] -To Assess the Preliminary Anti-Tumor Activity of LOXO-292 in Pediatric Participants with Tumors Harboring an Activating RET Alteration as Determined by ORR Based on RECIST v1.1 [ Time Frame: Up to 24 months ] -Changes from Baseline in Pain Measures as Measured by Wong Baker Faces scales. Wong-Baker Faces Pain Scale includes pictures of facial expressions with correlating scores of 0 being 'no hurt' and 10 being 'hurts worst'. -Changes from Baseline in Health Related Quality of Life Measures as Measured by Pediatric Quality of Life (PedsQoL) Inventory Core. PedsQoL includes a list of problems with scores of 0 being 'never a problem' and 4 being 'almost always a problem'. Phase 2 [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed. ] -Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator -Objective Response Rate as Assessed by RANO, as Assessed by Investigator -Duration of Response (DOR) as Assessed by Investigator -Duration of Response (DOR) as Assessed by IRC -Progression Free Survival (PFS) as Assessed by Investigator -PFS as Assessed by IRC -Overall survival (OS) -Clinical Benefit Rate (by Investigator) -Clinical Bene | — |
Countries
Australia, Canada, Denmark, France, Germany, Italy, Korea, Spain, United Kingdom, United States
Outcome results
None listed