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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03899792
Other study ID # 17493
Secondary ID J2G-OX-JZJJLOXO-
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date June 13, 2019
Est. completion date May 31, 2029

Study information

Verified date March 2024
Source Eli Lilly and Company
Contact There may be multiple sites in this clinical trial. 1-877-CTLILL
Phone 1-317-615-4559
Email ClinicalTrials.gov@lilly.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 information / eligibility

Status Recruiting
Enrollment 50
Est. completion date May 31, 2029
Est. primary completion date December 15, 2024
Accepts healthy volunteers No
Gender All
Age group 6 Months to 21 Years
Eligibility 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])

Study Design


Intervention

Drug:
LOXO-292
Oral LOXO-292

Locations

Country Name City State
Australia Royal Children's Hospital Parkville Victoria
Australia The Children's Hospital at Westmead Westmead New South Wales
Canada The Hospital for Sick Children Toronto Ontario
Denmark Rigshospitalet Copenhagen
France Gustave Roussy Villejuif Cedex
Germany Universitätsklinikum Heidelberg Heidelberg Baden-Württemberg
Italy Fondazione IRCCS Istituto Nazionale dei Tumori Milan Lombardia
Japan National Cancer Center Hospital Chuo-ku Tokyo
Japan Hiroshima University Hospital Hiroshima
Japan Kyoto University Hospital Kyoto
Japan Hokkaido University Hospital Sapporo Hokkaido
Korea, Republic of Seoul National University Hospital Seoul Seoul, Korea
Spain Hospital Universitari Vall d'Hebron Barcelona Barcelona [Barcelona]
United Kingdom University College Hospital - London London Greater London
United States The Children's Hospital for Cancer and Blood Disorders Aurora Colorado
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States University of Texas Southwestern Medical Center at Dallas Dallas Texas
United States Texas Childrens Hospital Houston Texas
United States Childrens Hospital of Los Angeles Los Angeles California
United States St. Jude Children's Research Hospital Memphis Tennessee
United States University Of Minnesota Hospital Minneapolis Minnesota
United States Memorial Sloan Kettering Cancer Center New York New York
United States Nemours Children's Health Orlando Florida
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Seattle Children's Hospital Research Foundation Seattle Washington

Sponsors (2)

Lead Sponsor Collaborator
Loxo Oncology, Inc. Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Denmark,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Advanced Solid Tumors: Dose Limiting Toxicities (DLTs) For Phase 1 During the first 28-day cycle of LOXO-292 treatment
Primary To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Primary CNS Tumors: DLTs For Phase 1 During the first 28-day cycle of LOXO-292 treatment
Primary Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Independent Review Committee (IRC) For Phase 2 Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
Primary ORR Based on Response Assessment in Neuro-Oncology (RANO) per IRC For Phase 2 Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
Secondary Plasma Concentrations of LOXO-292 Phase 1 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)
Secondary Area Under the Concentration-Time Curve from 0 to 24 hours (AUC0-24) of LOXO-292 Phase 1 and Phase 2 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)
Secondary Maximum Concentration (Cmax) of LOXO-292 Phase 1 and Phase 2 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)
Secondary Time to Maximum Concentration (Tmax) of LOXO-292 Phase 1 and Phase 2 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)
Secondary Recommended LOXO-292 Dose for Phase 2 (MTD) For Phase 1 Cycle 1 (28 days)
Secondary 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 For Phase 1 Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
Secondary 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 1 Up to 24 months
Secondary 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 1 Up to 24 months
Secondary Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator For Phase 2 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.
Secondary Objective Response Rate as Assessed by RANO, as Assessed by Investigator For Phase 2 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.
Secondary Duration of Response (DOR) as Assessed by Investigator For Phase 2 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.
Secondary Duration of Response (DOR) as Assessed by the IRC For Phase 2 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.
Secondary Progression Free Survival (PFS) as Assessed by Investigator For Phase 2 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.
Secondary PFS as Assessed by IRC For Phase 2 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.
Secondary Overall survival (OS) For Phase 2 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.
Secondary Clinical Benefit Rate (by Investigator) For Phase 2 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.
Secondary Clinical Benefit Rate (by IRC) For Phase 2 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.
Secondary Frequency of Adverse Events (AEs) For Phase 2 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)
Secondary To Evaluate the Concordance of Prior Molecular that Detected a RET Alteration within the Participant's Tumor with Diagnostic Tests Being Evaluated by Sponsor For Phase 2 6 months
Secondary 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) Up to 3 years
Secondary 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. Up to 3 years
Secondary Descriptive Analysis of Pretreatment Surgical Plan For Phase 2 Up to 3 years
Secondary Descriptive Analysis of Post-Treatment Plans For Phase 2 Up to 3 years
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