Clinical trial NCT04774718: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: ALK Fusion-positive Solid or CNS Tumors
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-03-01
Enrollment: 42
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Incidence of Participants with Dose-Limited Toxicities (DLTs)
timeFrame: Cycle 1 (cycle length = 28 days)
measure: Percentage of Participants with Adverse Events
timeFrame: Up to 10 years
measure: Plasma Concentration of Alectinib
timeFrame: Up to 10 years
measure: Plasma Concentration of Alectinib Metabolite (M4)
timeFrame: Up to 10 years
measure: 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)
timeFrame: Up to 10 years
Secondary outcomes:
measure: Confirmed ORR as Determined by the Investigator
timeFrame: Up to 10 years
measure: Duration of Response (DOR) as Determined by BICR and the Investigator
timeFrame: 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)
measure: Time to Response (TTR) as Determined by BICR and the Investigator
timeFrame: From the first dose of alectinib to the first documentation of objective response (CR or PR) (up to 10 years)
measure: Clinical Benefit Rate (CBR) as Determined by BICR and the Investigator
timeFrame: 6 months after the first dose of alectinib
measure: Progression-Free Survival (PFS) as Determined by BICR and the Investigator
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From the first dose of alectinib to the date of death due to any cause (up to 10 years)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan, C.S. Mott Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Children's Minnesota
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Memphis
country: United States
facility: St. Jude Children'S Research Hospital
state: Tennessee
city: Randwick
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Graacc-Grupo de Apoio ao adolescente e a crianca com cancer
state: São Paulo
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Beijing
country: China
facility: Beijing Children's Hospital, Capital Medical University
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Lyon
country: France
facility: Centre Léon Bérard, Institut d?Hémato-Oncologie Pédiatrique
city: Marseille
country: France
facility: Hôpital de la Timone, Oncologie Pédiatrique
city: Paris
country: France
facility: Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Genova
country: Italy
facility: Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS
state: Liguria
city: Milano
country: Italy
facility: Istituto Nazionale Tumori di Milano
state: Lombardia
city: Torino
country: Italy
facility: Dipartimento di Scienze Pediatriche Adolescenza
state: Piemonte
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Childrens Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Great North Children's Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital (Sutton)
Study officials:
affiliation: Hoffmann-LaRoche
name: Clinical Trials
role: STUDY_DIRECTOR
References: