Clinical trial • Phase I/II • Oncology
ALECTINIB for ALK fusion-positive solid tumors | ALK fusion-positive primary CNS tumors
Phase I/II trial of ALECTINIB for ALK fusion-positive solid tumors | ALK fusion-positive primary CNS tumors.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- ALK fusion-positive solid tumors | ALK fusion-positive primary CNS tumors
- Trial Stage
- Phase I/II
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 06-06-2024
- First CTIS Authorization Date
- 09-07-2024
Trial design
open-label, none/not specified-controlled, adaptive Phase I/II trial across 11 sites in Germany, Spain, Denmark and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Adaptive
- True, includes a safety run-in/dose confirmation (Part 1) to identify pediatric RP2D with a minimum of 6 participants (up to ~18) and dose refinement by modelling/simulation; expansion rules: initial expansion (Part 2) with minimum 10 participants and trigger for additional expansion if 4 or more participants achieve an objective response; integrated efficacy analysis across cohorts for confirmation.
- Biomarker Stratified
- True, biomarker: ALK gene fusions (ALK fusion-positive participants only)
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 32
Eligibility
Recruits 32 paediatric patients.
- Vulnerable Population
- Pediatric participants (<18 years) are included and the trial selects vulnerable populations (isVulnerablePopulationSelected=true). Age-appropriate subject information sheets, informed consent forms and assent forms are provided (documents for 3-6 years, 7-11 years, 12-17 years, parent/principal ICFs and assent forms are listed in the application documents). Parental/legal guardian consent is required for minors, and age-specific assent forms are available for children/adolescents as indicated by the submitted ICF/assent documents.
Inclusion criteria
- {"criterion_text":"- Age at study entry <18 years old"}
- {"criterion_text":"- 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"}
- {"criterion_text":"- Participants with prior treatment proven to be ineffective (relapsed or refractory), or for whom there is no satisfactory treatment available"}
- {"criterion_text":"- Participants with tumor tissue availability 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 willing to undergo a core or excisional biopsy sample collection prior to enrollment"}
- {"criterion_text":"- Adequate performance status (for participants < 16 years old: Lansky Performance Status should be >= 50% and for participants >= 16 years old: Karnofsky Performance Status should be >= 50%)"}
- {"criterion_text":"- Participants with adequate end-organ function"}
Exclusion criteria
- {"criterion_text":"- Medical history of prior use of ALK inhibitors, diagnosis of Anaplastic Large Cell Lymphoma (ALCL), any gastrointestinal (GI) disorder that may affect absorption of oral medications, organ transplant, recent stem cell infusions (with or without traumatic brain injury), hypersensitivity to any of the additives in the alectinib drug formulation, substance abuse within 12 months prior to screening, congenital bone disorders, bone metabolism alterations or osteopenia (familial or personal history), treatment with investigational therapy 28 days prior to initiation of study drug"}
- {"criterion_text":"- Liver disease as evidenced by abnormal levels of ALT or AST and Bilirubin"}
- {"criterion_text":"- Abnormal levels of creatinine or glomerular filtration rate (GFR)"}
- {"criterion_text":"- Co-administration of anti-cancer therapies other than those administered in this study"}
- {"criterion_text":"- Active hepatitis B or C virus (HBV, HBC) or known HIV positivity or AIDS-related illness"}
- {"criterion_text":"- Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the participant upon induction of neutropenia"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 1. Incidence of dose-limiting toxicities (DLTs) assessed during the first cycle of study treatment (Part 1 only)","definition_or_measurement_approach":"Assessed during the first cycle of study treatment in Part 1 (DLTs incidence during first cycle)."}
- {"endpoint_text":"- 2. Incidence and severity of adverse events, with severity determined according to the NCI-CTCAE v5.0, as well as changes from baseline in physical findings, targeted vital signs, clinical lab test results and ECG parameters (Part 1)","definition_or_measurement_approach":"Adverse events graded per NCI-CTCAE v5.0; changes from baseline in physical findings, specified vital signs, lab results and ECG parameters (Part 1)."}
- {"endpoint_text":"- 3. Plasma concentrations of alectinib and its metabolites (M4) at specified timepoints","definition_or_measurement_approach":"Pharmacokinetic sampling to measure plasma concentrations of alectinib and metabolite M4 at prespecified timepoints."}
- {"endpoint_text":"- 4. Confirmed objective response rate (ORR) as determined by blinded independent central review","definition_or_measurement_approach":"Confirmed ORR assessed by blinded independent central review (objective response per imaging/response criteria as specified in protocol)."}
Secondary endpoints
- {"endpoint_text":"- 1. Confirmed ORR as determined by the investigator","definition_or_measurement_approach":"Investigator-assessed confirmed objective response rate."}
- {"endpoint_text":"- 2. Duration of response (DOR)","definition_or_measurement_approach":"Time from initial response to progression or death (as per protocol definition)."}
- {"endpoint_text":"- 3. Time to response (TTR)","definition_or_measurement_approach":"Time from first dose to first documented response."}
- {"endpoint_text":"- 4. Clinical benefit rate (CBR)","definition_or_measurement_approach":"Proportion of participants achieving clinical benefit as defined in the protocol."}
- {"endpoint_text":"- 5. Progression-free survival (PFS) as determined by blinded independent central review and by the investigator","definition_or_measurement_approach":"PFS assessed both by blinded independent central review and investigator assessments."}
- {"endpoint_text":"- 6. Overall survival (OS)","definition_or_measurement_approach":"Time from first dose to death from any cause."}
- {"endpoint_text":"- 7. Incidence and severity of adverse events, with severity determined according to the NCI-CTCAE v5.0, as well as changes from baseline in physical findings, targeted vital signs, clinical lab test results and ECG parameters (Part 2 and 3)","definition_or_measurement_approach":"Adverse events graded per NCI-CTCAE v5.0; monitoring of changes from baseline in clinical and laboratory parameters for Parts 2 and 3."}
Recruitment
- Registry Or Advocacy Recruitment
- True, Innovative Therapies For Children With Cancer
- Planned Sample Size
- 32
- Recruitment Window Months
- 101
- Consent Approach
- Parental/legal guardian informed consent is required for minors; age-appropriate subject information sheets and assent forms are provided. The submission includes multiple age-specific ICFs and assent documents (e.g., ICFs and SIS for 3-6 years, 7-11 years, 12-17 years, parent/principal ICFs and assent forms). A Spanish-language assent document is present ('Asentimiento 12 a 17 anos') and multiple language versions of protocol/title translations exist; age-specific consent/assent procedures are used per site-specific ICFs.
Geography
- Total Number Of Sites
- 11
- Total Number Of Participants
- 23
Germany
- Earliest CTIS Part Ii Submission Date
- 26-06-2024
- Latest Decision Or Authorization Date
- 11-04-2025
- Processing Time Days
- 289
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Universitaetsklinikum Heidelberg AöR
- Department Name
- KiTZ Hopp-Kindertumorzentrum
- Principal Investigator Name
- Cornelis van Tilburg
- Principal Investigator Email
- cornelis.vantilburg@med.uni-heidelberg.de
- Contact Person Name
- Cornelis van Tilburg
- Contact Person Email
- cornelis.vantilburg@med.uni-heidelberg.de
Spain
- Earliest CTIS Part Ii Submission Date
- 26-06-2024
- Latest Decision Or Authorization Date
- 12-05-2026
- Processing Time Days
- 685
- Number Of Sites
- 3
- Number Of Participants
- 2
Sites
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- Oncología
- Principal Investigator Name
- José Luis Moreno Carrasco
- Principal Investigator Email
- josel.moreno.carrasco@juntadeandalucia.es
- Contact Person Name
- José Luis Moreno Carrasco
- Contact Person Email
- josel.moreno.carrasco@juntadeandalucia.es
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Oncología
- Principal Investigator Name
- María Adela Cañete Nieto
- Principal Investigator Email
- canyete_ade@gva.es
- Contact Person Name
- María Adela Cañete Nieto
- Contact Person Email
- canyete_ade@gva.es
- Site Name
- Hospital Infantil Universitario Nino Jesus
- Department Name
- Oncología
- Principal Investigator Name
- Alvaro Lassaletta Atienza
- Principal Investigator Email
- alvaro.lassaletta@salud.madrid.org
- Contact Person Name
- Alvaro Lassaletta Atienza
- Contact Person Email
- alvaro.lassaletta@salud.madrid.org
Denmark
- Earliest CTIS Part Ii Submission Date
- 26-06-2024
- Latest Decision Or Authorization Date
- 08-05-2026
- Processing Time Days
- 681
- Number Of Sites
- 1
- Number Of Participants
- 9
Sites
- Site Name
- Rigshospitalet
- Department Name
- Børne og Unge Afdelingen
- Principal Investigator Name
- Karsten Nysom
- Principal Investigator Email
- karsten.nysom@regionh.dk
- Contact Person Name
- Karsten Nysom
- Contact Person Email
- karsten.nysom@regionh.dk
France
- Earliest CTIS Part Ii Submission Date
- 26-06-2024
- Latest Decision Or Authorization Date
- 12-05-2026
- Processing Time Days
- 685
- Number Of Sites
- 3
- Number Of Participants
- 6
Sites
- Site Name
- Institut Curie
- Department Name
- Department of Pediatric Oncology
- Principal Investigator Name
- Francois Doz
- Principal Investigator Email
- francois.doz@curie.fr
- Contact Person Name
- Francois Doz
- Contact Person Email
- francois.doz@curie.fr
- Site Name
- Centre Leon Berard
- Department Name
- Department of Pediatric Oncology
- Principal Investigator Name
- Nadege Corradini
- Principal Investigator Email
- Nadege.CORRADINI@ihope.fr
- Contact Person Name
- Nadege Corradini
- Contact Person Email
- Nadege.CORRADINI@ihope.fr
- Site Name
- Centre Hospitalier Regional De Marseille
- Department Name
- Department of Pediatric Oncology
- Principal Investigator Name
- Andre Nicolas
- Principal Investigator Email
- nicolas.andre@ap-hm.fr
- Contact Person Name
- Andre Nicolas
- Contact Person Email
- nicolas.andre@ap-hm.fr
Italy
- Earliest CTIS Part Ii Submission Date
- 26-06-2024
- Latest Decision Or Authorization Date
- 12-05-2026
- Processing Time Days
- 685
- Number Of Sites
- 3
- Number Of Participants
- 4
Sites
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- Oncologia pediatrica
- Principal Investigator Name
- Michela Casanova
- Principal Investigator Email
- michela.casanova@istitutotumori.mi.it
- Contact Person Name
- Michela Casanova
- Contact Person Email
- michela.casanova@istitutotumori.mi.it
- Site Name
- Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
- Department Name
- Dipartimento di Scienze Pediatriche Adolescenza
- Principal Investigator Name
- Franca Fagioli
- Principal Investigator Email
- franca.fagioli@unito.it
- Contact Person Name
- Franca Fagioli
- Contact Person Email
- franca.fagioli@unito.it
- Site Name
- Giannina Gaslini Institute For Scientific Hospitalization And Care
- Department Name
- Oncologia pediatrica
- Principal Investigator Name
- Carla Manzitti
- Principal Investigator Email
- carlamanzitti@gaslini.org
- Contact Person Name
- Carla Manzitti
- Contact Person Email
- carlamanzitti@gaslini.org
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Iqvia Inc.
- Responsibilities
- Monitoring
- Name
- Fortrea Inc.
- Responsibilities
- Other Third Party Duty
- Name
- Signant Health Global LLC
- Responsibilities
- Other Third Party Duty
Third parties
- {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Other Third Party Duty","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"MARKEN Germany GmbH","duties_or_roles":"Other Third Party Duty","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Signant Health Management Limited","duties_or_roles":"code:3","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Other Third Party Duty","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"WORLDCARE CLINICAL","duties_or_roles":"Other Third Party Duty","organisation_type":"Health care"}
- {"country":"United States","full_name":"Iqvia Inc.","duties_or_roles":"Monitoring","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"DHL Supply Chain Operations GmbH","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Innovative Therapies For Children With Cancer","duties_or_roles":"code:2","organisation_type":"Industry"}
- {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Other Third Party Duty","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- ALECTINIB
- Active Substance
- ALECTINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
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