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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04774718

Collaborator

(none)

Enrollment

Locations

Arm

105.6

Anticipated Duration (Months)

2.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
ALK Fusion-positive Solid or CNS Tumors	Drug: Alectinib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 14, 2021

Anticipated Primary Completion Date :

Jun 7, 2026

Anticipated Study Completion Date :

Jul 3, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALK-Fusion Positive 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 Participants will receive twice-daily alectinib capsules on Days 1-28 of each 28-day cycle

Arm

Intervention/Treatment

Experimental: ALK-Fusion Positive

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

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

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Histologically confirmed diagnosis of CNS or solid tumors harboring ALK gene fusions as determined locally by an appropriately validated assay performed in a CLIA-certified or equivalently-accredited diagnostic laboratory, or centrally by a Foundation Medicine Clinical Trial Assay (CTA) or the alternative, approved central laboratory for that region
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; 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
2	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
3	Sydney Children's Hospital	Randwick	New South Wales	Australia	2031
4	Royal Children's Hospital	Parkville	Victoria	Australia	3052
5	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
6	CHU Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
7	Rigshospitalet; Ny Medicin til Børn med Kræft	København Ø		Denmark	2100
8	Centre Léon Bérard, Institut d'Hémato-Oncologie Pédiatrique	Lyon		France	69373
9	Hôpital de la Timone, Oncologie Pédiatrique	Marseille		France	13385
10	Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris; Service d Oncologie Pediatrique	Paris		France	75248
11	Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS	Genova	Liguria	Italy	16147
12	Istituto Nazionale Tumori di Milano; S.C. Oncologia Pediatrica	Milano	Lombardia	Italy	20133
13	Dipartimento di Scienze Pediatriche Adolescenza; Osp. Infantile Regina Margherita	Torino	Piemonte	Italy	10126
14	Seoul National University Hospital	Seoul		Korea, Republic of	03080
15	Asan Medical Center	Seoul		Korea, Republic of	05505
16	Samsung Medical Center	Seoul		Korea, Republic of	06351
17	Hospital Infantil Universitario Nino Jesus	Madrid		Spain	28009
18	Hospital Universitari i Politecnic La Fe	Valencia		Spain	46026

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-LaRoche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT04774718

Other Study ID Numbers:

GO42286
2020-004239-25

First Posted:

Mar 1, 2021

Last Update Posted:

Aug 22, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Central Nervous System Neoplasms

Study Results

No Results Posted as of Aug 22, 2022