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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03899792




Registration number
NCT03899792
Ethics application status
Date submitted
6/02/2019
Date registered
2/04/2019

Titles & IDs
Public title
A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors
Scientific 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
Secondary ID [1] 0 0
J2G-OX-JZJJ
Secondary ID [2] 0 0
17493
Universal Trial Number (UTN)
Trial acronym
LIBRETTO-121
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medullary Thyroid Cancer 0 0
Infantile Myofibromatosis 0 0
Infantile Fibrosarcoma 0 0
Papillary Thyroid Cancer 0 0
Soft Tissue Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Thyroid
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - LOXO-292

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


Treatment: Drugs: LOXO-292
Oral LOXO-292
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Advanced Solid Tumors: Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
During the first 28-day cycle of LOXO-292 treatment
Primary outcome [2] 0 0
To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Primary CNS Tumors: DLTs
Timepoint [2] 0 0
During the first 28-day cycle of LOXO-292 treatment
Primary outcome [3] 0 0
Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Independent Review Committee (IRC)
Timepoint [3] 0 0
Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
Primary outcome [4] 0 0
ORR Based on Response Assessment in Neuro-Oncology (RANO) per IRC
Timepoint [4] 0 0
Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
Secondary outcome [1] 0 0
Plasma Concentrations of LOXO-292
Timepoint [1] 0 0
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 outcome [2] 0 0
Area Under the Concentration-Time Curve from 0 to 24 hours (AUC0-24) of LOXO-292
Timepoint [2] 0 0
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 outcome [3] 0 0
Maximum Concentration (Cmax) of LOXO-292
Timepoint [3] 0 0
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 outcome [4] 0 0
Time to Maximum Concentration (Tmax) of LOXO-292
Timepoint [4] 0 0
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 outcome [5] 0 0
Recommended LOXO-292 Dose for Phase 2 (MTD)
Timepoint [5] 0 0
Cycle 1 (28 days)
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)
Secondary outcome [7] 0 0
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'.
Timepoint [7] 0 0
Up to 24 months
Secondary outcome [8] 0 0
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'.
Timepoint [8] 0 0
Up to 24 months
Secondary outcome [9] 0 0
Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator
Timepoint [9] 0 0
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 outcome [10] 0 0
Objective Response Rate as Assessed by RANO, as Assessed by Investigator
Timepoint [10] 0 0
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 outcome [11] 0 0
Duration of Response (DOR) as Assessed by Investigator
Timepoint [11] 0 0
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 outcome [12] 0 0
Duration of Response (DOR) as Assessed by the IRC
Timepoint [12] 0 0
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 outcome [13] 0 0
Progression Free Survival (PFS) as Assessed by Investigator
Timepoint [13] 0 0
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 outcome [14] 0 0
PFS as Assessed by IRC
Timepoint [14] 0 0
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 outcome [15] 0 0
Overall survival (OS)
Timepoint [15] 0 0
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 outcome [16] 0 0
Clinical Benefit Rate (by Investigator)
Timepoint [16] 0 0
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 outcome [17] 0 0
Clinical Benefit Rate (by IRC)
Timepoint [17] 0 0
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 outcome [18] 0 0
Frequency of Adverse Events (AEs)
Timepoint [18] 0 0
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 outcome [19] 0 0
To Evaluate the Concordance of Prior Molecular that Detected a RET Alteration within the Participant's Tumor with Diagnostic Tests Being Evaluated by Sponsor
Timepoint [19] 0 0
6 months
Secondary outcome [20] 0 0
Phase 2: Post-Operative Stage on Participants Treated with LOXO-292
Timepoint [20] 0 0
Up to 3 years
Secondary outcome [21] 0 0
Phase 2: Surgical Margin Status in Participants Treated with LOXO-292
Timepoint [21] 0 0
Up to 3 years
Secondary outcome [22] 0 0
Descriptive Analysis of Pretreatment Surgical Plan
Timepoint [22] 0 0
Up to 3 years
Secondary outcome [23] 0 0
Descriptive Analysis of Post-Treatment Plans
Timepoint [23] 0 0
Up to 3 years

Eligibility
Key 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
Minimum age
6 Months
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/05/2029
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Denmark
State/province [13] 0 0
Copenhagen
Country [14] 0 0
France
State/province [14] 0 0
Villejuif Cedex
Country [15] 0 0
Germany
State/province [15] 0 0
Baden-Württemberg
Country [16] 0 0
Italy
State/province [16] 0 0
Lombardia
Country [17] 0 0
Japan
State/province [17] 0 0
Hokkaido
Country [18] 0 0
Japan
State/province [18] 0 0
Tokyo
Country [19] 0 0
Japan
State/province [19] 0 0
Hiroshima
Country [20] 0 0
Japan
State/province [20] 0 0
Kyoto
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul, Korea
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona [Barcelona]
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Greater London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Loxo Oncology, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
Address 0 0
Country 0 0
Phone 0 0
1-317-615-4559
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03899792