A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Alectinib in Pediatric Participants With ALK Fusion-Positive Solid or CNS Tumors

Study Overview
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Brief Summary
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This study will evaluate the safety, pharmacokinetics, and efficacy of alectinib in children and adolescents with ALK fusion-positive solid or CNS tumors for whom prior treatment has proven to be ineffective or for whom there is no satisfactory standard treatment available.

Official Title
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A Phase I/II, Open-Label, Multicenter, Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Alectinib in Pediatric Participants With ALK Fusion-Positive Solid or CNS Tumors for Whom Prior Treatment Has Proven to be Ineffective or for Whom There is No Satisfactory Treatment Available

Conditions
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ALK Fusion-positive Solid or CNS Tumors

Intervention / Treatment
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* Drug: Alectinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically confirmed diagnosis of CNS or solid tumors with documented evidence of ALK gene fusions as assessed centrally through the use of the investigational F1CDx assay or based on pre-existing NGS test results Disease status: prior treatment proven to be ineffective (i.e. relapsed or refractory), or for whom there is no satisfactory standard treatment available. Disease should be measurable and evaluable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, or Response Assessment in Neuro-oncology criteria (RANO) +/- bone marrow criteria for primary CNS tumors or International Neuroblastoma Response Criteria (INRC) Available tumor tissue for submission to the Sponsor from active disease, obtained subsequent to last anti-cancer therapy regiment administered and obtained prior to study enrollment, or willingness to undergo a core or excisional biopsy sample collection prior to enrollment For participants < 16 years old, Lansky Performance Status >/= 50% For participants >/= 16 years old, Karnofsky Performance Status >/= 50% Adequate bone marrow function as defined by the protocol within at least 28 days prior to initiation of study drug Participant and/or caregiver willingness and ability to complete clinical outcome assessments throughout the study using either electronic, paper, or interviewer methods For females of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, as defined by the protocol For males who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm, as defined by the protocol Exclusion Criteria Medical history of: prior use of ALK inhibitors; diagnosis of Anaplastic Large Cell Lymphoma (ALCL); any gastrointestinal disorder that may affect absorption of oral medications, such as mal-absorption syndrome or status post-major bowel resection; history of organ transplant; stem cell infusions as defined by the protocol Substance abuse within 12 months prior to screening Familial or personal history of congenital bone disorders, bone metabolism alterations, or osteopenia Treatment with investigational therapy 28 days prior to initiation of study drug Liver or kidney disease as defined by the protocol National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade >/=3 toxicities attributed to any prior therapy such as radiotherapy (excluding alopecia), which have not shown improvement and are strictly considered to interfere with alectinib Co-administration of anti-cancer therapies other than those administered in this study Active hepatitis B or C virus (HBV, HBC), or known HIV-positivity or AIDS-related illness Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the participant in this study Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; such conditions should be discussed with the participant before trial entry Planned procedure or surgery during the study except as permitted treatment as defined by the protocol Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the participant upon induction of neutropenia, including participants who are, or should be, on antimicrobial agents for the treatment as active infection Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of alectinib

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALK-Fusion Positive<br>Part 1 is a dose-confirmation phase to confirm the recommended phase 2 dose (RP2D). In Parts 2 and 3, participants will receive alectinib at the RP2D on Days 1-28 of each 28-day cycle | Drug: Alectinib<br>* Participants will receive twice-daily alectinib capsules on Days 1-28 of each 28-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Participants with Dose-Limited Toxicities (DLTs) |  | Cycle 1 (cycle length = 28 days) | 
| Percentage of Participants with Adverse Events |  | Up to 10 years | 
| Plasma Concentration of Alectinib |  | Up to 10 years | 
| Plasma Concentration of Alectinib Metabolite (M4) |  | Up to 10 years | 
| Confirmed Objective Response Rate (ORR): Defined as the Proportion of Participants with Complete Response (CR) or Partial Response (PR) on two Consecutive Occasions >/= 4 Weeks Apart, as Determined by Blinded Independent Central Review (BICR) |  | Up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed ORR as Determined by the Investigator |  | Up to 10 years | 
| Duration of Response (DOR) as Determined by BICR and the Investigator |  | From the first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause, whichever occurs first (up to 10 years) | 
| Time to Response (TTR) as Determined by BICR and the Investigator |  | From the first dose of alectinib to the first documentation of objective response (CR or PR) (up to 10 years) | 
| Clinical Benefit Rate (CBR) as Determined by BICR and the Investigator |  | 6 months after the first dose of alectinib | 
| Progression-Free Survival (PFS) as Determined by BICR and the Investigator |  | From the first dose of alectinib to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 10 years) | 
| Overall Survival (OS) |  | From the first dose of alectinib to the date of death due to any cause (up to 10 years) |