A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors
- Conditions
- Infantile FibrosarcomaSoft Tissue SarcomaInfantile MyofibromatosisMedullary Thyroid CancerPapillary Thyroid Cancer
- Interventions
- Registration Number
- NCT03899792
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
This is an open-label, multi-center Phase 1/2 study of oral LOXO-292 in pediatric participants with an activating rearranged during transfection (RET) alteration and an advanced solid or primary CNS tumor.
- Detailed Description
This study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). In phase 1, participants will be enrolled using a rolling 6 dose escalation scheme. The starting dose of LOXO-292 is equivalent to the adult recommended phase 2 dose of 160 milligrams (mg) twice a day (BID). Once the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) is identified, participants will be enrolled to one of four phase 2 dose expansion cohorts depending on tumor histology and tumor genotype. Cycle length will be 28 days.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 50
- 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
- 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])
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LOXO-292 LOXO-292 Phase 1- Dose Escalation and determination of MTD; multiple dose levels of LOXO-292 to be evaluated; Phase 2 - The MTD/recommended dose from Phase 1
- Primary Outcome Measures
Name Time Method To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Advanced Solid Tumors: Dose Limiting Toxicities (DLTs) During the first 28-day cycle of LOXO-292 treatment For Phase 1
ORR Based on Response Assessment in Neuro-Oncology (RANO) per IRC Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months) For Phase 2
Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Independent Review Committee (IRC) Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months) For Phase 2
To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Primary CNS Tumors: DLTs During the first 28-day cycle of LOXO-292 treatment For Phase 1
- Secondary Outcome Measures
Name Time Method Plasma Concentrations of LOXO-292 Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days) Phase 1
Overall survival (OS) 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. For Phase 2
Duration of Response (DOR) as Assessed by the IRC 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. For Phase 2
Phase 2: Surgical Margin Status in Participants Treated with LOXO-292 Up to 3 years Tumor margins after surgery are classified into four groups using the International Cancer Control (UICC)-R classification and the Intergroup Rhabdomyosarcoma Staging (IRS) systems: 1) Complete tumor resection with histologically free margins, 2) Macroscopic resection but invaded margins on histology, 3)Macroscopic residual tumor and 4) Distant metastatic tumor.
Descriptive Analysis of Post-Treatment Plans Up to 3 years For Phase 2
Area Under the Concentration-Time Curve from 0 to 24 hours (AUC0-24) of LOXO-292 Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days) Phase 1 and Phase 2
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'. Up to 24 months For Phase 1
Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator 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. For Phase 2
Objective Response Rate as Assessed by RANO, as Assessed by Investigator 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. For Phase 2
Maximum Concentration (Cmax) of LOXO-292 Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days) Phase 1 and Phase 2
Time to Maximum Concentration (Tmax) of LOXO-292 Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days) Phase 1 and Phase 2
Recommended LOXO-292 Dose for Phase 2 (MTD) Cycle 1 (28 days) For Phase 1
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 Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months) For Phase 1
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'. Up to 24 months For Phase 1
Duration of Response (DOR) as Assessed by Investigator 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. For Phase 2
PFS as Assessed by IRC 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. For Phase 2
Clinical Benefit Rate (by IRC) Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed. For Phase 2
Progression Free Survival (PFS) as Assessed by Investigator 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. For Phase 2
Clinical Benefit Rate (by Investigator) Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed. For Phase 2
Frequency of Adverse Events (AEs) From the time of informed consent, for approximately 24 months (or earlier if the participants discontinues from the study), and through Safety Follow-up (28 days after the last dose) For Phase 2
To Evaluate the Concordance of Prior Molecular that Detected a RET Alteration within the Participant's Tumor with Diagnostic Tests Being Evaluated by Sponsor 6 months For Phase 2
Phase 2: Post-Operative Stage on Participants Treated with LOXO-292 Up to 3 years Tumor stage is described according to the Tumor, Node, Metastasis (TNM)Classification of malignant tumors of the Union for International Cancer Control (UICC)
Descriptive Analysis of Pretreatment Surgical Plan Up to 3 years For Phase 2
Trial Locations
- Locations (26)
University of Minnesota Hospital
🇺🇸Minneapolis, Minnesota, United States
Childrens Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
The Children's Hospital for Cancer and Blood Disorders
🇺🇸Aurora, Colorado, United States
Nemours Children's Health
🇺🇸Orlando, Florida, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
Texas Childrens Hospital
🇺🇸Houston, Texas, United States
Seattle Children's Hospital Research Foundation
🇺🇸Seattle, Washington, United States
The Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Royal Children's Hospital
🇦🇺Melbourne, Victoria, Australia
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Rigshospitalet
🇩🇰Copenhagen, Denmark
Gustave Roussy
🇫🇷Villejuif Cedex, France
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, Lombardia, Italy
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Hiroshima University Hospital
🇯🇵Hiroshima, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Korea, Republic of
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [Barcelona], Spain
University College Hospital - London
🇬🇧London, Greater London, United Kingdom