KOMET - Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas (D134BC00001)

Studio Clinico

Patologia: Altre neoplasie

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Richiesta mandatoria di tessuto: No

Linee di trattamento: Non applicabile

Criteri di inclusione: 

- Adults ≥ 18 years at enrollment with diagnosis of NF1 with symptomatic, inoperable PN
- At least one inoperable target PN measurable by volumetric MRI analysis
- Chronic target PN pain score documented for minimum period during screening period
- Stable chronic PN pain medication use at enrollment
- Adequate organ and marrow function

Criteri di esclusione: 

- Confirmed or suspected malignant glioma or MPNST (optic glioma not requiring chemotherapy or radiation therapy are exempt from this exclusion).
- History of malignancy except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence.
- Clinically significant cardiovascular disease, including inherited coronary disease, acute coronary syndrome within 6 months prior to enrollment, uncontrolled angina, symptomatic heart failure, cardiomyopathy, severe valvular heart disease, abnormal LVEF and uncontrolled hypertension.
- Ophthalmological findings/conditions including intraocular pressure > 21 mmHg, RPED/CSR or RVO
- Prior exposure to MEK inhibitors.

Trattamento sperimentale: 

Arm A = Selumetinib
Arm B = Placebo

Trattamento di controllo: 

Placebo

Obiettivi primari dello studio: 

Confirmed Objective Response Rate (ORR) for Arm A [ Time Frame: Approximately 3 years ]
ORR will be defined as the proportion of patients who have a confirmed complete response or confirmed partial response as determined by ICR per REiNS criteria.

Obiettivi secondari dello studio: 

- Change in chronic target PN pain intensity from baseline for Arm A versus Arm B as assessed using a PRO questionnaire [ Time Frame: Approximately 3 years ]
Difference in mean change from baseline in chronic target PN pain intensity score between Arm A and Arm B, obtained using an NRS-11 scale to assess pain intensity of a target plexiform neurofibroma
- Duration of response (DoR) for Arm A [ Time Frame: Approximately 3 years ]
DoR will be defined as the time from the date of first documented response (which is subsequently confirmed) until progression by ICR per REiNS criteria or death due to any cause
- Progression Free Survival (PFS) for Arm A [ Time Frame: Approximately 3 years ]
- PFS will be defined as the time from first selumetinib dose until date of disease progression by ICR per REiNS criteria or death due to any cause
- Time to progression (TTP) for Arm A [ Time Frame: Approximately 3 years ]
TTP is defined as the time from the date of first selumetinib dose until date of disease progression by ICR per REiNS criteria
- Time to Response (TTR) for Arm A [ Time Frame: Approximately 3 years ]
TTR is defined as the time from date of first selumetinib dose until the date of objective response by ICR per REiNS criteria
- Target PN volume for Arm A vs Arm B [ Time Frame: Approximately 3 years ]
Difference in best percentage change from baseline in target PN volume by ICR per REiNS criteria
- Physical functioning assessed using PROMIS physical function items [ Time Frame: Approximately 3 years ]
Difference in change from baseline between Arm A and Arm B
- Health Related Quality of Life (HRQoL) outcomes assessed using PlexiQoL [ Time Frame: Approximately 3 years ]
Difference in change from baseline between Arm A and Arm B.

Data di inizio dell'arruolamento: 19.11.2021

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2020-005607-39

Data di inserimento: 24.02.2022

Promotore

AstraZeneca

Principal Investigator ITALIA

Istituto Neurologico Carlo Besta, Milano

Riferimento: Dr.ssa Marica Eoli

Telefono: 0223942285

Email: neuroncologia.molecolare@istituto-besta.it

Localita: Milano