Clinical Trials Register

Summary
EudraCT Number:	2020-004239-25
Sponsor's Protocol Code Number:	GO42286
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-08
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-004239-25

A.3

Full title of the trial

A PHASE I/II, OPEN-LABEL, MULTICENTER STUDY EVALUATING THE SAFETY, PHARMACOKINETICS, AND EFFICACY OF ALECTINIB IN PEDIATRIC PATIENTS 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

STUDIO DI FASE I/II IN APERTO, MULTICENTRICO, PER VALUTARE LA SICUREZZA, LA FARMACOCINETICA E L’EFFICACIA DI ALECTINIB IN PAZIENTI PEDIATRICI AFFETTI DA NEOPLASIE SOLIDE O DEL SNC POSITIVE ALLA FUSIONE DI ALK, NEI QUALI IL PRECEDENTE TRATTAMENTO SI SIA RIVELATO INEFFICACE O PER I QUALI NON SIANO DISPONIBILI TERAPIE STANDARD SODDISFACENTI

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Alectinib in Pediatric Patients with Anaplastic Lymphoma Kinase (ALK) Fusion-Positive Solid or Central Nervous System (CNS) Tumors

Studio per valutare la sicurezza, farmacocinetica, ed efficacia di Alectinib in pazienti pediatrici affetti da tumori solidi o del SNC positivi alla fusione di ALK (Chinasi del Linfoma Anaplastico)

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

GO42286

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	F. HOFFMANN - LA ROCHE LTD.
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	F.Hoffmann-La Roche Ltd.
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F.Hoffmann-La Roche Ltd.
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	CH-4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	000000
B.5.5	Fax number	000000
B.5.6	E-mail	global.rochegenentechtrials@roche.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Alectinib
D.3.2	Product code	[Ro 542-4802]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALECTINIB
D.3.9.2	Current sponsor code	Ro 542-4802/F03-02
D.3.9.3	Other descriptive name	ALECTINIB Ro 542-4802/F03-02
D.3.9.4	EV Substance Code	SUB178557
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Alecensa
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH - Marketing Auth.: EU/1/16/1169/001 e EU/1/16/1169/002
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Alectinib
D.3.2	Product code	[Ro 542-4802]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALECTINIB
D.3.9.2	Current sponsor code	Ro 542-4802/F16-01
D.3.9.3	Other descriptive name	ALECTINIB Ro 542-4802/F16-01
D.3.9.4	EV Substance Code	SUB178557
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Alectinib
D.3.2	Product code	[Ro 542-4802]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALECTINIB
D.3.9.2	Current sponsor code	Ro 542-4802/F01-01
D.3.9.3	Other descriptive name	ALECTINIB Ro 542-4802/F01-01
D.3.9.4	EV Substance Code	SUB178557
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

ALK fusion-positive extracranial solid or primary CNS tumors who have progressed following prior treatment or who have no satisfactory treatment available

Neoplasie solide extracraniche o tumori primari del SNC positive alla fusione di ALK nei quali il precedente trattamento si sia rivelato inefficace e per i quali non siano disponibili terapie standard soddisfacenti

E.1.1.1

Medical condition in easily understood language

Solid tumors are masses of abnormal tissue growth that originate in organs or soft tissues and do not include fluid areas and cysts

I tumori solidi sono delle masse di tessuto cresciuto in modo anormale che si originano negli organi o nei tessuti molli e che non includono aree fluide e cisti

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10028992
E.1.2	Term	Neoplasm CNS
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10065252
E.1.2	Term	Solid tumor
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To confirm the recommended Phase II dose (RP2D) in pediatric patients as the dose equivalent matching adult exposure without dose-limiting toxicity (DLT)
• To evaluate the safety and tolerability of alectinib as a single agent
• To characterize the pharmacokinetics of alectinib and its major metabolite M4 and to confirm the pediatric RP2D
• To evaluate the anti-cancer activity of alectinib at the pediatric RP2D dose

• Confermare la dose raccomandata per la fase II (RP2D) in pazienti pediatrici come dose equivalente che determini la stessa esposizione degli adulti senza tossicità dose limitanti (DLT)
• Valutare la sicurezza e la tollerabilità di alectinib in monoterapia
• Caratterizzare la farmacocinetica di alectinib e del suo principale metabolita M4 e confermare la RP2D pediatrica
• Valutare l’attività antitumorale di alectinib alla dose RP2D pediatrica

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of alectinib in all enrolled patients receiving alectinib at the pediatric RP2D, in CNS patients and in solid patients.
• To evaluate the safety of single-agent alectinib on growth and development
• To evaluate potential relationships between drug exposure and the efficacy and safety of alectinib

• Valutare l’efficacia di alectinib in tutti i pazienti arruolati e trattati con alectinib alla RP2D pediatrica, nei pazienti con tumori del SNC e solidi
• Valutare la sicurezza di alectinib in monoterapia sulla crescita e lo sviluppo
• Valutare le potenziali relazioni tra esposizione al farmaco ed efficacia e sicurezza di alectinib

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age at study entry <18 years old
• 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
• Patients with prior treatment proven to be ineffective (relapsed or refractory), or for whom there is no satisfactory standard treatment available
• Patients 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, or willing to undergo a core or excisional biopsy sample collection prior to enrollment
• Life expectancy >=8 weeks, in the investigator's judgment
• Adequate performance status (For patients < 16 years old: Lansky Performance Status should be >= 50% and for patients >= 16 years old: Karnofsky Performance Status should be >= 50%)
• Patients with adequate end-organ function
• Females of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs during the treatment period and for at least 3 months after the final dose of study drug
• Females of childbearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation
• Males who are not surgically sterile must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm, during the treatment period and for at least 3 months after the final dose of study drug

• Età all’ingresso nello studio < 18 anni
• Diagnosi confermata istologicamente di neoplasia solida o del SNC che presenti la fusioni del gene ALK in base a quanto stabilito localmente mediante test debitamente validato effettuato in un laboratorio diagnostico dotato di certificazione CLIA o equivalente, oppure centralmente mediante un saggio per sperimentazione clinica di Foundation Medicine o in alternativa presso un laboratorio centrale approvato per la regione
• Precedente trattamento rivelatosi inefficace (malattia recidivata o refrattaria) o mancata disponibilità di una terapia standard soddisfacente
• Disponibilità di tessuto tumorale da presentare allo sponsor, prelevato da un sito di malattia attiva dopo l’ultima terapia antitumorale e prima dell’arruolamento nello studio o volontà di sottoporsi al prelievo di un campione mediante agobiopsia o biopsia escissionale prima dell’arruolamento
• Aspettativa di vita >=8 settimane, secondo il giudizio dello sperimentatore
• Performance status adeguato (Pazienti di età < 16 anni: performance Status secondo Lansky >= 50% e per Pazienti di età >= 16 anni: performance status secondo Karnofsky >= 50%)
• Adeguata funzione degli organi terminali
• Per le donne in età fertile: consenso a praticare l’astinenza (astenersi dai rapporti eterosessuali) o a utilizzare metodi contraccettivi e consenso ad astenersi dal donare ovuli durante il periodo di trattamento e per almeno 3 mesi dopo l’ultima dose del farmaco in studio
• Le pazienti di sesso femminile devono avere un risultato negativo al test di gravidanza sul siero effettuato durante lo screening e non devono allattare al seno né pianificare una gravidanza durante la partecipazione allo studio
• Per i pazienti di sesso maschile non sottoposti a sterilizzazione chirurgica: consenso a praticare l’astinenza (evitare i rapporti eterosessuali) o a utilizzare misure contraccettive e consenso ad astenersi dal donare il liquido seminale durante il periodo di trattamento e per almeno 3 mesi dopo l’ultima dose di alectinib

E.4

Principal exclusion criteria

• Medical history of prior use of ALK inhibitors, any gastrointestinal (GI) disorder that may affect absorption of oral medications, organ transplant, recent stem cell infusions (with or without traumatic brain injury)
• History of hypersensitivity to any of the additives in the alectinib drug formulation to be used in the study
• Substance abuse within 12 months prior to screening, in the investigator's judgment
• 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 disease
• Abnormal levels of creatinine or glomerular filtration rate (GFR)
• National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-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 human immunodeficiency virus (HIV) positivity or Acquired immunodeficiency syndrome (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 patient in this study
• Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures
• Planned procedure or surgery during the study except as permitted treatment
• Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the patient upon induction of neutropenia such as fungal infection or bacterial infection or neutropenic fever or patients who have received <5 days of appropriate therapeutic antibiotic therapy for an identified infection
• Pregnant or breastfeeding women, or intending to become pregnant during the study or within 3 months after the final dose of alectinib

• Anamnesi di precedente utilizzo di inibitori di ALK, qualsiasi disturbo GI che potrebbe influire sull’assorbimento di medicinali orali, trapianto d’organo, recenti infusioni di cellule staminali (con o senza lesione cerebrale traumatica)
• Anamnesi di ipersensibilità a uno qualsiasi degli additivi presenti nella formulazione di alectinib da utilizzare nello studio
• Abuso di sostanze nei 12 mesi precedenti lo screening, secondo il giudizio dello sperimentatore
• Storia familiare o personale di disturbi ossei congeniti, alterazioni del metabolismo osseo o osteopenia
• Trattamento con una terapia sperimentale nei 28 giorni precedenti l’avvio del farmaco in studio
• Epatopatia
• Livelli anomali di creatinina o velocità di filtrazione glomerulare stimata (GFR)
• Tossicità di grado NCI CTCAE v 5.0 >=3 attributed to any prior therapy such as radiotherapy (excluding alopecia), attribuite a un qualsiasi trattamento precedente come ad esempio la radioterapia (esclusa alopecia), che non hanno fatto rilevare un miglioramento e che si ritiene interferiscano con alectinib
• Somministrazione concomitante di terapie antineoplastiche diverse da quelle somministrate in questo studio
• Infezione attiva da virus dell’epatite B o C (HBV, HBC) o nota positività all’HIV o alle malattie correlate all’AIDS
• Qualsiasi patologia o affezione concomitante clinicamente significativa che potrebbe interferire con (o essere influenzata da) il trattamento dello studio, la conduzione dello studio o l’assorbimento di medicinali orali o che potrebbe, secondo il parere dello sperimentatore principale, porre a rischio inaccettabile il paziente coinvolto nello studio
• Qualsiasi situazione psicologica, familiare, sociologica o geografica che potrebbe ostacolare il rispetto dei requisiti del protocollo di studio e/o delle procedure di follow-up
• Procedura o intervento chirurgico programmati durante lo studio, eccetto quelli consentiti dal trattamento
• Infezione ritenuta dallo sperimentatore non clinicamente controllata o che ponga il paziente a rischio inaccettabile in seguito all’induzione di neutropenia come infezione fungina o batterica o febbre neutropenica o pazinti sottoposti a meno di 5 giorni di terapia antibiotica appropriata per un’infezione identificata
• Gravidanza o allattamento, o gravidanza pianificata durante lo studio o nei 3 mesi successivi all’ultima dose di alectinib

E.5 End points

E.5.1

Primary end point(s)

1. Incidence of dose-limiting toxicities (DLTs) assessed during the first cycle of study treatment
2. Incidence and severity of adverse events by 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
3. Plasma concentrations of alectinib and its metabolites (M4) at specified timepoints
4. Confirmed objective response rate (ORR) as determined by blinded independent central review

1. Incidenza di DLT, valutata durante il primo ciclo di trattamento dello studio
2. Incidenza e gravità degli eventi avversi, determinando la gravità in base ai criteri NCI CTCAE v 5.0, così come variazioni rispetto al basale dei riscontri all’esame obiettivo, di parametri vitali mirati, dei risultati di determinate analisi cliniche di laboratorio e di di determinati parametri dell’ECG
3. Concentrazioni plasmatiche di alectinib e del suo metabolita (M4) in punti temporali specifici
4. Tasso di risposta obiettiva confermato (ORR) stabilita mediante revisione centralizzata indipendente in cieco (BICR)

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Assessment during the first cycle
2-3. Baseline to 5 years
4. When a minimum of 10 and 30 pediatric patients have been enrolled in the expansion portion of the study and followed for at least 6 months, respectively.

1. Valutazione durante il primo ciclo
2-3. Dal Basale a 5 anni
4. Quando un minimo di 10 e 30 pazienti pediatrici sono stati arruolati nella porzione di espansione dello studio e seguiti per almeno 6 mesi, rispettivamente.

E.5.2

Secondary end point(s)

1. Key efficacy endpoint; Confirmed ORR as determined by the investigator, Duration of response (DOR), Time to response (TTR), Clinical benefit rate (CBR), as determined by blinded independent central review and by the investigator
2. Overall survival (OS)
3. Change from baseline in growth patterns (relative to age specific standards for height, weight, and head circumference), in development patterns and neurocognitive outcome (using age-appropriate measures/scales)
4. Relationship between plasma concentration or PK parameters for alectinib and efficacy or safety endpoints

1. Endpoint chiave di efficacia; ORR confermato secondo il giudizio dello sperimentatore, Durata della risposta (DOR), Tempo di risposta (TTR), Tasso di beneficio clinico (CBR), secondo la valutazione BICR e dello sperimentatore
2. Sopravvivenza complessiva (OS)
3. Variazione rispetto al basale delle curve di crescita (rispetto agli standard specifici per l’età di altezza, peso e circonferenza cranica), delle curve di sviluppo ed esiti neurocognitivi (utilizzando parametri appropriati per l’età)
4. Relazione tra concentrazione plasmatica o parametri di PK di alectinib ed endpoint di efficacia o sicurezza

E.5.2.1

Timepoint(s) of evaluation of this end point

1-4. When a minimum of 10 and 30 pediatric patients have been enrolled in the expansion portion of the study and followed for at least 6 months, respectively. When patients have been followed up to 5 years.

1-4. Quando un minimo di 10 e 30 pazienti pediatrici è stato arruolato nella porzione di espansione dello studio e seguito per almeno 6 mesi, rispettivamente. Quando i pazienti sono stati sequiti per almento 5 anni.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

I/II

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

In aperto

Open

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

China

Hong Kong

Korea, Republic of

United States

Denmark

France

Germany

Italy

Spain

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of this study is defined as the date when the last patient, last visit occurs (LPLV) or 5 years after the last patient is enrolled and treated with study drug, whichever occurs first. For an individual patient, the completion of the study (i.e., the last visit) will occur when the patient withdraws consent, has completed follow-up, has been lost to followup, dies, or when the study is stopped.

La fine dello studio sarà la data di esecuzione dell’ultima visita dell’ultimo paziente (LPLV) oppure avrà luogo 5 anni dopo che l’ultimo paziente sarà stato arruolato e trattato con il farmaco in studio, a seconda dell’evento che si verificherà prima. Per il singolo paziente, la conclusione dello studio (ossia l’ultima visita) avrà luogo quando il paziente revocherà il consenso, avrà completato il follow-up, sarà perso al follow-up, sarà deceduto o quando lo studio sarà interrotto.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Paediatric patients and brain affected patients

Pazienti pediatrici e pazienti colpiti al cervello

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The Sponsor will offer continued access to Roche IMP (alectinib) free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, as outlined in protocol 4.2.5.
The Roche Global Policy on Continued Access to Investigational Medicinal Product is available at the following website:
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf

Lo Sponsor continuerà a offrire gratuitamente l’accesso all’IMP Roche (alectinib) ai pazienti eleggibili in accordo alle Policy Globali Roche sull’accesso continuato all’IMP, come definito nella sez. 4.2.5 del protocollo.
La Policy Globale Roche sull’accesso continuato all’IMP è disponibile al seguente link:
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	ITCC
G.4.3.4	Network Country	France

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-07-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-27

P. End of Trial
P.	End of Trial Status	Ongoing

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Select Trial Status:	Select Trial Phase:
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Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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