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Active, Not Recruiting

NCT Number: NCT03899792

A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Medullary Thyroid Cancer Adenocarcinoma Adenocarcinoma, Papillary Breast Diseases Breast Neoplasms Bronchial Diseases Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Medullary Carcinoma, Neuroendocrine Carcinoma, Non-Small-Cell Lung Central Nervous System Neoplasms Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Infantile Fibrosarcoma Infantile Myofibromatosis Intestinal Diseases Intestinal Neoplasms Lung Diseases Lung Neoplasms Myofibromatosis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Ductal, Lobular, and Medullary Neoplasms, Fibrous Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Nervous System Diseases Nervous System Neoplasms Neuroectodermal Tumors Neuroendocrine Tumors Papillary Thyroid Cancer Respiratory Tract Diseases Respiratory Tract Neoplasms Sarcoma Skin Diseases Skin and Connective Tissue Diseases Soft Tissue Sarcoma Thoracic Neoplasms Thyroid Cancer, Papillary Thyroid Diseases Thyroid Neoplasms

Age range

6 month–21 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

The Children's Hospital at Westmead, Westmead, New South Wales, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

  • 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])

Treatment and study plan

Selpercatinib

Drug

Oral LOXO-292

Other names: LOXO-292, LY3527723

Primary outcomes

  1. Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

    Time frame: Cycle 1 (28 Day Cycle)

    A DLT was any of the adverse events that starts on or after the first administration of study drug listed below, as defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.

    • Any Grade(G) ≥3 nonhematologic toxicity except G3 fatigue, nausea, tendon reflex decrease, weight gain attributable to normal growth and development.
    • G3 vomiting/diarrhea was DLT only if it persists >48 h despite standard of care treatment.
    • G4 vomiting/diarrhea was DLT regardless of duration.
    • Any toxicity, regardless of the NCI CTCAE v5.0 grade, resulting in discontinuation or dose reduction of treatment (except symptoms related to progressive disease (PD)).
    • G4/G3 thrombocytopenia with G1 or higher bleeding.
    • G4 anemia lasting >8 days, despite supportive therapy.
    • G4 neutropenia, lasting >8 days, despite supportive therapy

  2. Phase 2: Percentage of Participants With Overall Response Rate (ORR) in Study

    Time frame: Date of first dose to disease progression or death (Up to 62.4 Months)

    ORR: Percentage of participants who achieve best overall response Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST).

    • CR is defined as disappearance of all target lesions.
    • PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Secondary outcomes

  1. Plasma Concentrations of LOXO-292

    Time frame: 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)

    Outcome data will be provided after the study is completed.

  2. Area Under the Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of LOXO-292

    Time frame: 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)

    Outcome data will be provided after the study is completed.

  3. Maximum Concentration (Cmax) of LOXO-292

    Time frame: 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)

    Outcome data will be provided after the study is completed.

  4. Time to Maximum Concentration (Tmax) of LOXO-292

    Time frame: 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)

    Outcome data will be provided after the study is completed.

  5. Recommended LOXO-292 Dose for Phase 2 (MTD)

    Time frame: Cycle 1 (28 days)

    Outcome data will be provided after the study is completed.

  6. 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: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)

    Outcome data will be provided after the study is completed.

  7. 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'.

    Time frame: Up to 24 months

    Outcome data will be provided after the study is completed.

  8. 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'.

    Time frame: Up to 24 months

    Outcome data will be provided after the study is completed.

  9. Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator

    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.

    Outcome data will be provided after the study is completed.

  10. Objective Response Rate as Assessed by RANO, as Assessed by Investigator

    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.

    Outcome data will be provided after the study is completed.

  11. Duration of Response (DOR) as Assessed by Investigator

    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.

    Outcome data will be provided after the study is completed.

  12. Duration of Response (DOR) as Assessed by the IRC

    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.

    Outcome data will be provided after the study is completed.

  13. Progression Free Survival (PFS) as Assessed by Investigator

    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.

    Outcome data will be provided after the study is completed.

  14. PFS as Assessed by IRC

    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.

    Outcome data will be provided after the study is completed.

  15. Overall Survival (OS)

    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.

    Outcome data will be provided after the study is completed.

  16. Clinical Benefit Rate (by Investigator)

    Time frame: 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.

    Outcome data will be provided after the study is completed.

  17. Clinical Benefit Rate (by IRC)

    Time frame: 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.

    Outcome data will be provided after the study is completed.

  18. Frequency of Adverse Events (AEs)

    Time frame: 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)

    Outcome data will be provided after the study is completed.

  19. To Evaluate the Concordance of Prior Molecular That Detected a RET Alteration Within the Participant's Tumor With Diagnostic Tests Being Evaluated by Sponsor

    Time frame: 6 months

    Outcome data will be provided after the study is completed.

  20. Phase 2: Post-Operative Stage on Participants Treated With LOXO-292

    Time frame: 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). Outcome data will be provided after the study is completed.

  21. Phase 2: Surgical Margin Status in Participants Treated With LOXO-292

    Time frame: 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. Outcome data will be provided after the study is completed.

  22. Descriptive Analysis of Pretreatment Surgical Plan

    Time frame: Up to 3 years

    Outcome data will be provided after the study is completed.

  23. Descriptive Analysis of Post-Treatment Plans

    Time frame: Up to 3 years

    Outcome data will be provided after the study is completed.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Collaborators

  • Loxo Oncology, Inc.

Registry information

Official study title

A Phase 1/2 Study of the Oral RET Inhibitor LOXO 292 in Pediatric Patients With Advanced RET-Altered Solid or Primary Central Nervous System Tumors

Acronym: LIBRETTO-121

Important dates

Study start
2019
Primary completion
2024
Study completion
2029
First posted
Apr 2, 2019
Registry last updated
Jan 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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