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

Soft Tissue Sarcoma Clinical Trial

— LIBRETTO-121  

Official 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

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
• 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
• 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])

Related Conditions & MeSH terms

• Fibrosarcoma
• Infantile Fibrosarcoma
• Infantile Myofibromatosis
• Medullary Thyroid Cancer
• Papillary Thyroid Cancer
• Sarcoma
• Soft Tissue Sarcoma
• Thyroid Cancer, Papillary
• Thyroid Diseases
• Thyroid Neoplasms

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