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

Phase 2Active Not RecruitingNCT03899792

Eli Lilly and Company36 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Medullary Thyroid Cancer Infantile Myofibromatosis Infantile Fibrosarcoma Papillary Thyroid Cancer Soft Tissue Sarcoma

Interventions

SelpercatinibDRUG

Oral LOXO-292

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 21 Years

Medical Language ↔ Plain English

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\[s\])

Locations (26)

Outcomes

Primary Outcomes

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

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

Time frame: Cycle 1 (28 Day Cycle)

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

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.

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

Secondary Outcomes

Plasma Concentrations of LOXO-292

Outcome data will be provided after the study is completed.

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)

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

Outcome data will be provided after the study is completed.

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)

Data from ClinicalTrials.gov

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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

University of Minnesota Hospital

Minneapolis, Minnesota, 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

...and 16 more locations

Maximum Concentration (Cmax) of LOXO-292

Outcome data will be provided after the study is completed.

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)

Time to Maximum Concentration (Tmax) of LOXO-292

Outcome data will be provided after the study is completed.

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)

Recommended LOXO-292 Dose for Phase 2 (MTD)

Outcome data will be provided after the study is completed.

Time frame: Cycle 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 v1.1

Outcome data will be provided after the study is completed.

Time frame: Baseline 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'.

Outcome data will be provided after the study is completed.

Time frame: Up 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'.

Outcome data will be provided after the study is completed.

Time frame: Up to 24 months

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

Outcome data will be provided after the study is completed.

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 RANO, as Assessed by Investigator

Outcome data will be provided after the study is completed.

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.

Duration of Response (DOR) as Assessed by Investigator

Outcome data will be provided after the study is completed.

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.

Duration of Response (DOR) as Assessed by the IRC

Outcome data will be provided after the study is completed.

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.

Progression Free Survival (PFS) as Assessed by Investigator

Outcome data will be provided after the study is completed.

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.

PFS as Assessed by IRC

Outcome data will be provided after the study is completed.

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.

Overall Survival (OS)

Outcome data will be provided after the study is completed.

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.

Clinical Benefit Rate (by Investigator)

Outcome data will be provided after the study is completed.

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.

Clinical Benefit Rate (by IRC)

Outcome data will be provided after the study is completed.

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.

Frequency of Adverse Events (AEs)

Outcome data will be provided after the study is completed.

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)

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

Outcome data will be provided after the study is completed.

Time frame: 6 months

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

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.

Time frame: Up to 3 years

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

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.

Time frame: Up to 3 years

Descriptive Analysis of Pretreatment Surgical Plan

Outcome data will be provided after the study is completed.

Time frame: Up to 3 years

Descriptive Analysis of Post-Treatment Plans

Outcome data will be provided after the study is completed.

Time frame: Up to 3 years