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JOURNAL ONKOLOGIE – STUDIE

PASS of Paediatric Patients Initiating Selumetinib

Rekrutierend

NCT-Nummer:
NCT05388370

Studienbeginn:
Mai 2022

Letztes Update:
05.04.2024

Wirkstoff:
-

Indikation (Clinical Trials):
Neurofibromatoses, Neurofibromatosis 1, Neurofibroma

Geschlecht:
Alle

Altersgruppe:
Kinder (0-17)

Phase:
-

Sponsor:
AstraZeneca

Collaborator:
-

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com» Kontaktdaten anzeigen

Studienlocations
(3 von 39)

Research Site
Duisburg
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
Tubingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

Neurofibromatosis type 1 (NF1) is a rare, autosomal dominant genetic disorder that is caused

by germline mutations in the NF1 tumour suppressor gene, which encodes the tumour suppressor

protein neurofibromin 1. Plexiform neurofibromas (PN) are histologically benign nerve sheath

tumours, which typically grow along large nerves and plexi.

On 5 March 2020, a centralized Marketing Authorisation Application was submitted to the

European Medicines Agency (EMA), Marketing Authorization in EU was granted on 17 Jun 2021.

As part of the approval process, a Risk Management Plan (RMP) was developed and submitted to

the EMA to summarise the safety concerns emerging from the clinical development program. The

RMP included additional pharmacovigilance plans for a non-interventional Post-authorisation

Safety Study (PASS) to further characterise the safety of selumetinib in paediatric patients

with NF1-related PN in routine clinical practice.

The RMP version 1.0 (succession 4) approved by EMA on 22 April 2021 had 1 important

identified risk with selumetinib treatment:

-LVEF reduction

The RMP also identified 5 important potential risks with selumetinib treatment:

- Physeal dysplasia

- Ocular toxicity

- Myopathy

- Hepatotoxicity

- Choking on the capsule Long-term exposure (including long-term safety data on

developmental toxicity in children) was identified in the RMP as an area of missing

information.

The planned non-interventional PASS will address gaps in knowledge identified by the RMP,

including the important identified risk and some of the potential risks and missing

information on long-term developmental toxicity in children, by characterising the safety

profile associated with selumetinib use among paediatric patients (aged d 8 to < 18 years

old) with a diagnosis of NF1 with symptomatic, inoperable PN.

This study is a specific obligation in the context of a conditional marketing authorisation

for selumetinib (ie, Category 2 PASS). Study results will contribute to updating the safety

profile of selumetinib in a relatively large population of patients with different personal

characteristics across multiple health care systems and patterns of real-world clinical

practice in up to 52 specialist clinics for the treatment of pediatric patients with NF1

across up to 12 European countries and in Israel.

The primary objective of this study is:

- To characterise the safety of selumetinib, including up to 6 years of long-term safety, in

paediatric patients with NF1-related symptomatic, inoperable PN, 8 to < 18 years old who have

not reached Tanner Stage V at the start of selumetinib treatment (Nested Prospective Cohort).

The secondary objective of this study is:

- To describe the demographic and clinical profile of the paediatric population 3 to < 18

years old with NF1-related symptomatic inoperable PN who start selumetinib in routine

clinical practice (Base Cohort).

The study observation period was anticipated to begin in Q2 of 2022, with some variation by

country (actual start date was 23 May 2022). Patients will be enrolled after selumetinib

access is commercially available and patients are able to receive the medicine as part of

local clinical practice.

The target population for this study are patients with NF1 in the EU with symptomatic,

inoperable PN who have been prescribed at least 1 dose of selumetinib and who are aged 3 to <

18 years at the start of selumetinib treatment, except for those patients receiving treatment

with a mitogen-activated protein kinase inhibitor before the index date.

The study will enrol 2 cohorts:

1. The Base Cohort includes all enrolled patients aged 3 to < 18 years.

2. The Nested Prospective Cohort will include the subset of Base Cohort patients aged 8 to

< 18 years who have not reached Tanner Stage V on the index date.

Patient screening will be conducted throughout the enrolment period and baseline data for all

patients will be abstracted from medical records. Those meeting the criteria for enrolment in

the Nested Prospective Cohort will be followed up during their routine standard of care

visits with the treating clinician (expected to occur every 6 to 12 months) for up to 6

years.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Have been diagnosed with NF1 with symptomatic, inoperable PN

- Have initial treatment with selumetinib up to 6 months (i.e.182 days)prior to

enrolment into the study (i.e. signature of the ICF)

- Are aged 3 years and above, and are < 18 years of age on the index date

- Parent or legal guardian, as required by country-specific regulation, have provided

informed consent (unless a country-specific waiver is obtained) Additional Criteria

for Nested Prospective Cohort

- Are at least 8 years old and

- Are prior to attainment of Tanner Stage V on the index date

Exclusion Criteria:

- Have received treatment with a mitogen-activated protein kinase inhibitor before the

index date

- Are participating in an interventional study at index date

Studien-Rationale

Primary outcome:

1. LVEF reduction (Time Frame - at routine clinical care throughout the follow up, with frequency of 6 to 12 months):
LVEF reduction will be detected as present or absent and when present if symptomatic or asymptomatic. All cardiac tests conducted will be collected Measured on routine echocardiogram or a cardiac MRI (CT, angiography, etc.) and then collected into the study from the medical records.

2. Occurrence of Physeal dysplasia after treatment start (Time Frame - at routine clinical care throughout the follow up, with frequency of 6 to 12 months):
Physeal dysplasia will be detected as present or absent based on the physician reading of: MRI: Knee (preferred) or wrist X-ray: Knee (preferred) and/or wrist to assess growth plate Height and weight records

3. Rise of serum creatine phosphokinase levels AND concurrent musculoskeletal symptoms (Time Frame - at routine clinical care throughout the follow up, with frequency of 6 to 12 months, up to 6 years):
A clinically meaningful rise in serum creatine phosphokinase (eg, above the normal limit or increase by 1 or more CTCAE grade shift) combined with musculoskeletal symptoms will be detected as present or absent based on the physician's reading, as a marker of potential myopathy

4. Rise in transaminase (ALT and AST) and concurrent rise in bilirubin (Time Frame - at routine clinical care throughout the follow up, with frequency of 6 to 12 months, up to 6 years):
A clinically meaningful rise in the measured levels (eg, above the normal limit or increase by 1 or more CTCAE grade shift) will be detected as present or absent, and when present if symptomatic or asymptomatic, as a marker of potential hepatotoxicity

5. Cumulative incidence of ocular toxicity (Time Frame - at routine clinical care throughout the follow up, with frequency of 6 to 12 months):
An abnormal ocular examination will be detected as present or absent based on the physician's reading, as a marker of potential ocular toxicity

6. Cumulative incidence of Abnormal pubertal development (Time Frame - at routine clinical care throughout the follow up, with frequency of 6 to 12 months):
Tanner stage criteria (Stages I-V). Abnormal pubertal development will require interpretation by the Investigator with respect to Tanner Stage in the context of the patient's age; recorded as normal or abnormal (if abnormal, further specified as delayed puberty or precocious puberty)

Secondary outcome:

1. baseline data - demographics (Time Frame - At baseline - most recent assessments made within 365 days before the index date):
Demographics: Age

2. baseline data - demographics (Time Frame - At baseline - most recent assessments made within 365 days before the index date):
sex

3. baseline data - demographics (Time Frame - At baseline - most recent assessments made within 365 days before the index date):
height (cm)

4. baseline data - demographics (Time Frame - At baseline - most recent assessments made within 365 days before the index date):
weight (kg)

5. baseline data - demographics (Time Frame - At baseline - most recent assessments made within 365 days before the index date):
Tanner staging level

6. baseline data - demographics (Time Frame - At baseline - most recent assessments made within 365 days before the index date):
Ethnicity (where allowed by GDPR/privacy laws)

7. Baseline data - Clinical characteristics (Time Frame - At baseline - most recent assessments made within 365 days before the index date):
PN(s) (number, location, classification and morbidities)

8. Baseline data - Clinical characteristics (Time Frame - At baseline - most recent assessments made within 365 days before the index date):
prior medication and relevant procedures, concomitant medications

9. Baseline data - Clinical characteristics (Time Frame - At baseline - most recent assessments made within 365 days before the index date):
date of initial NF1 and PN diagnosis, NF1 origin (familial or spontaneous), and any genetic testing results

Studien-Arme

  • Base Cohort
    The Base Cohort includes all enrolled patients aged 3 to < 18 years.
  • Nested Prospective Cohort
    The Nested Prospective Cohort will include the subset of Base Cohort patients aged 8 to < 18 years who have not reached Tanner Stage V on the index date

Quelle: ClinicalTrials.gov


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