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

PHASE1PHASE2RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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])

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Eligibility

Age eligible for study : 6 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2019-06-13

Primary completion: 2024-12-15

Study completion finish: 2029-05-31

Study type

TREATMENT

Phase

PHASE1

PHASE2

Trial ID

NCT03899792

Intervention or treatment

DRUG: LOXO-292

Conditions

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

Image related to Medullary Thyroid Cancer

Condition: Medullary Thyroid Cancer, Infantile Myofibromatosis and more
DRUG: LOXO-292
Westmead, New South Wales, Australia and more
Sponsor: Loxo Oncology, Inc.

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

The Children's Hospital at Westmead

Research sites nearby

Select from list below to view details:

The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Royal Children's Hospital
Parkville, Victoria, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
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	DRUG: LOXO-292 Oral LOXO-292

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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
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
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)
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
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)
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)
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)
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)
Recommended LOXO-292 Dose for Phase 2 (MTD)	For Phase 1	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	For Phase 1	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'.	For Phase 1	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'.	For Phase 1	Up to 24 months
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.
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.
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.
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.
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.
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.
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.
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.
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.
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)
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
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
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
Descriptive Analysis of Pretreatment Surgical Plan	For Phase 2	Up to 3 years
Descriptive Analysis of Post-Treatment Plans	For Phase 2	Up to 3 years

Frequently Asked Questions

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References

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