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

• ClinicalTrials.gov Identifier: NCT04774718
• Recruitment Status: Recruiting
• First Posted: March 1, 2021
• Last Update Posted: May 26, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: February 10, 2021
• First Posted Date: March 1, 2021
• Last Update Posted Date: May 26, 2023
• Actual Study Start Date: September 14, 2021
• Estimated Primary Completion Date: June 7, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 17, 2021)

• 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 ]

Original Primary Outcome Measures (submitted: February 25, 2021)

• 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 8 years ]
• Plasma Concentration of Alectinib [ Time Frame: Up to 8 years ]
• Plasma Concentration of Alectinib Metabolite (M4) [ Time Frame: Up to 8 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 8 years ]

Current Secondary Outcome Measures (submitted: June 17, 2021)

• 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) ]

Original Secondary Outcome Measures (submitted: February 25, 2021)

• Confirmed ORR as Determined by the Investigator [ Time Frame: Up to 8 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 8 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 8 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 8 years) ]
• Overall Survival (OS) [ Time Frame: From the first dose of alectinib to the date of death due to any cause (up to 8 years) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: ALK Fusion-positive Solid or CNS Tumors

Intervention

Drug: Alectinib

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

Study Arms

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

Intervention: Drug: Alectinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 25, 2021): 42
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 3, 2030
• Estimated Primary Completion Date: June 7, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: GO42286 https://forpatients.roche.com/; 888-662-6728; global-roche-genentech-trials@gene.com

• Listed Location Countries: Australia, Canada, China, Denmark, France, Italy, Korea, Republic of, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04774718
• Other Study ID Numbers: GO42286; 2020-004239-25 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-LaRoche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2023