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

PHASE1PHASE2RECRUITING

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.

info
Simpliy with AI

Study details:

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.

info
Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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])
  • info
    Simplify with AI

    Eligibility

    Age eligible for study : 6 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2019-06-13

    Primary completion: 2024-12-15

    Study completion finish: 2029-05-31

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE1

      PHASE2

    trial

    Trial ID

    NCT03899792

    Intervention or treatment

    DRUG: LOXO-292

    Conditions

    • Medullary Thyroid Cancer
    • Infantile Myofibromatosis
    • Infantile Fibrosarcoma
    • Papillary Thyroid Cancer
    • Soft Tissue Sarcoma
    Image related to Medullary Thyroid Cancer
    • Condition: Medullary Thyroid Cancer, Infantile Myofibromatosis and more

    • DRUG: LOXO-292

    • Westmead, New South Wales, Australia and more

    • Sponsor: Loxo Oncology, Inc.

    Find a site

    Closest Location:

    The Children's Hospital at Westmead

    Research sites nearby

    Select from list below to view details:

    • The Children's Hospital at Westmead

      Westmead, New South Wales, Australia

    • Royal Children's Hospital

      Parkville, Victoria, Australia

    Loading...

    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: 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
    DRUG: LOXO-292
    • Oral LOXO-292

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Advanced Solid Tumors: Dose Limiting Toxicities (DLTs)For Phase 1During the first 28-day cycle of LOXO-292 treatment
    To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Primary CNS Tumors: DLTsFor Phase 1During the first 28-day cycle of LOXO-292 treatment
    Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Independent Review Committee (IRC)For Phase 2Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
    ORR Based on Response Assessment in Neuro-Oncology (RANO) per IRCFor Phase 2Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Plasma Concentrations of LOXO-292Phase 1Days 1 and 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-292Phase 1 and Phase 2Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)
    Maximum Concentration (Cmax) of LOXO-292Phase 1 and Phase 2Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)
    Time to Maximum Concentration (Tmax) of LOXO-292Phase 1 and Phase 2Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)
    Recommended LOXO-292 Dose for Phase 2 (MTD)For Phase 1Cycle 1 (28 days)
    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 v1.1For Phase 1Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 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'.For Phase 1Up to 24 months
    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'.For Phase 1Up to 24 months
    Objective Response Rate as Assessed by RECIST v1.1, as Assessed by InvestigatorFor Phase 2Approximately 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 RANO, as Assessed by InvestigatorFor Phase 2Approximately 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.
    Duration of Response (DOR) as Assessed by InvestigatorFor Phase 2Approximately 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.
    Duration of Response (DOR) as Assessed by the IRCFor Phase 2Approximately 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.
    Progression Free Survival (PFS) as Assessed by InvestigatorFor Phase 2Approximately 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.
    PFS as Assessed by IRCFor Phase 2Approximately 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.
    Overall survival (OS)For Phase 2Approximately 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.
    Clinical Benefit Rate (by Investigator)For Phase 2Approximately 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.
    Clinical Benefit Rate (by IRC)For Phase 2Approximately 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.
    Frequency of Adverse Events (AEs)For Phase 2From 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)
    To Evaluate the Concordance of Prior Molecular that Detected a RET Alteration within the Participant's Tumor with Diagnostic Tests Being Evaluated by SponsorFor Phase 26 months
    Phase 2: Post-Operative Stage on Participants Treated with LOXO-292Tumor stage is described according to the Tumor, Node, Metastasis (TNM)Classification of malignant tumors of the Union for International Cancer Control (UICC)Up to 3 years
    Phase 2: Surgical Margin Status in Participants Treated with LOXO-292Tumor 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.Up to 3 years
    Descriptive Analysis of Pretreatment Surgical PlanFor Phase 2Up to 3 years
    Descriptive Analysis of Post-Treatment PlansFor Phase 2Up to 3 years

    Frequently Asked Questions

    Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

    No questions submitted. Be the first to ask a question!

    You may be eligible to participate in this trial based on your search.Apply for study
    Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

    References

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

    Other trails to consider

    Top searched conditions