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

Official title

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

Overview

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.

Interventions

• Drug Alectinib
  Participants will receive twice-daily alectinib capsules on Days 1-28 of each 28-day cycle

Primary outcome measures

• Incidence of Participants with Dose-Limited Toxicities (DLTs) [Time frame: Cycle 1 (cycle length = 28 days)]
• Percentage of Participants with Adverse Events [Time frame: Up to 10 years]
• Plasma Concentration of Alectinib [Time frame: Up to 10 years]
• Plasma Concentration of Alectinib Metabolite (M4) [Time frame: 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) [Time frame: Up to 10 years]

Secondary outcome measures (6)

• Confirmed ORR as Determined by the Investigator [Time frame: Up to 10 years]
• Duration of Response (DOR) as Determined by BICR and the Investigator [Time frame: 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 [Time frame: 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 [Time frame: 6 months after the first dose of alectinib]
• Progression-Free Survival (PFS) as Determined by BICR and the Investigator [Time frame: 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) [Time frame: From the first dose of alectinib to the date of death due to any cause (up to 10 years)]

Eligibility criteria

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 regimen administered and obtained prior to study enrollment (preferred option), or archival tumor tissue from original diagnosis, 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Lucile Packard Children's Hospital — Palo Alto
• Johns Hopkins All Children's Hospital — St. Petersburg
• University of Michigan, C.S. Mott Children's Hospital — Ann Arbor
• Children's Minnesota — Minneapolis
• Memorial Sloan Kettering Cancer Center — New York
• Cincinnati Children's Hospital Medical Center — Cincinnati
• St. Jude Children'S Research Hospital — Memphis

United Kingdom · 4 centers

• Great Ormond Street Hospital — London
• Royal Manchester Childrens Hospital — Manchester
• Great North Children's Hospital — Newcastle upon Tyne
• Royal Marsden Hospital (Sutton) — Sutton

France · 3 centers

• Centre Léon Bérard, Institut d?Hémato-Oncologie Pédiatrique — Lyon
• Hôpital de la Timone, Oncologie Pédiatrique — Marseille
• Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris — Paris

Italy · 3 centers

• Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS — Genoa
• Istituto Nazionale Tumori di Milano — Milan
• Dipartimento di Scienze Pediatriche Adolescenza — Turin

South Korea · 3 centers

• Seoul National University Hospital — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

Spain · 3 centers

• Hospital Infantil Universitario Nino Jesus — Madrid
• Hospital Universitario Virgen del Rocio — Seville
• Hospital Universitari i Politecnic La Fe — Valencia

Australia · 2 centers

• Sydney Children's Hospital — Randwick
• Royal Children's Hospital — Parkville

Brazil · 2 centers

• Hospital de Cancer de Barretos — Barretos
• Graacc-Grupo de Apoio ao adolescente e a crianca com cancer — São Paulo

Canada · 2 centers

• The Hospital for Sick Children — Toronto
• CHU Sainte-Justine — Montreal

China · 2 centers

• Beijing Children's Hospital, Capital Medical University — Beijing
• Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai

Denmark · 1 center

• Rigshospitalet — København Ø

Germany · 1 center

• Universitätsklinikum Heidelberg — Heidelberg

Publications

• Bagchi A, Chiang J, Pinto S, Dhanda S, Gajjar A. Infant-Type Hemispheric Gliomas: A Review of Clinical, Radiologic, Histopathologic, and Molecular Features. J Natl Compr Canc Netw. 2025 Nov;23(11):e257064. doi: 10.6004/jnccn.2025.7064. PMID 41213248

Identifiers

NCT: NCT04774718 · GO42286 · 2020-004239-25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗