Soft Tissue Sarcoma Clinical Trial
— LIBRETTO-121Official 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
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.
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]) |
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 |
Lead Sponsor | Collaborator |
---|---|
Loxo Oncology, Inc. | Eli Lilly and Company |
United States, Australia, Canada, Denmark, France, Germany, Italy, Japan, Korea, Republic of, Spain, United Kingdom,
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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