Etude : AcceleRET / BLU-667-2303



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Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : AcceleRET / BLU-667-2303

Situation thérapeutique : Métastatique ou localement avancé

Traitement : Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 06/12/2021
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Étude de phase 3, en ouvert, randomisée, visant à comparer le pralsetinib aux soins standards pour le traitement de première ligne du cancer du poumon non à petites cellules métastatique positif à la fusion RET

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C34 - Tumeur maligne des bronches et du poumon
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : This is an international, randomized, open-label, Phase 3 study designed to evaluate whether the potent and selective RET inhibitor, pralsetinib, improves outcome when compared to a platinum chemotherapy-based regimen chosen by the Investigator from a list of standard of care treatments, as measured primarily by progression free survival (PFS), for patients with RET fusion-positive metastatic NSCLC who have not previously received systemic anticancer therapy for metastatic disease. Patients who have centrally confirmed progressive disease on the control arm have the option to crossover to pralsetinib.

STUDY ARMS:
- Experimental: Pralsetinib
Patients randomized to the Experimental Arm will receive pralsetinib

- Active Comparator: Platinum doublet with or without pembrolizumab
Patients randomized to the Active Comparator Arm will receive 1 of 6 platinum-based chemotherapy treatment regimens (with or without pembrolizumab) at the study center as chosen by the treating Investigator (based on histology).
* Nonsquamous histology:
** Carboplatin or cisplatin / pemetrexed (with vitamin supplementation); with optional pemetrexed (with vitamin supplementation) maintenance.
** Pembrolizumab / carboplatin or cisplatin / pemetrexed (with vitamin supplementation); followed by pembrolizumab and optional pemetrexed (with vitamin supplementation) maintenance.
* Squamous histology:
** Carboplatin or cisplatin / gemcitabine

CURRENT PRIMARY OUTCOME:
Progression Free Survival (PFS) [ Time Frame: Estimated at up to 32 months ]

CURRENT SECONDARY OUTCOMES:
- Overall Response Rate (ORR) [ Time Frame: Estimated at up to 32 months ]
- Overall Survival (OS) [ Time Frame: Estimated at approximately 32 months ]
- Number of patients with adverse events and serious adverse events [ Time Frame: Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months) ]
- Changes in Eastern Cooperative Oncology Group Performance Status (ECOG PS) [ Time Frame: Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months) ]
- Duration of Response (DOR) [ Time Frame: Estimated at up to 32 months ]
- Clinical Benefit Rate (CBR) [ Time Frame: Estimated at up to 32 months ]
- Disease Control Rate (DCR) [ Time Frame: Estimated at up to 32 months ]
- Time to intracranial progression in accordance with RECIST 1.1 criteria [ Time Frame: Estimated at up to 32 months ]
- Intracranial response rate in accordance with RECIST 1.1 criteria [ Time Frame: Estimated at up to 32 months ]
- European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-C30 Questionnaires [ Time Frame: From baseline until progressive disease or death (estimated 32 months) ]
- European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-LC13 Scores [ Time Frame: From baseline until progressive disease or death (estimated 32 months) ]
- EuroQoL 5 Dimension (EQ-5D-5L) Assessment [ Time Frame: From baseline until progressive disease or death (estimated 32 months) ]
- Plasma drug concentration at specified time points of pralsetinib [ Time Frame: Assessed every 3 weeks, up to 9 weeks from baseline ]

Phase : III

Stade : Localement avancé à Métastatique

1
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : Main inclusion criteria:
- Patient is ≥18 years of age
- Patient has pathologically confirmed, definitively diagnosed, advanced (not able to be treated with surgery or radiotherapy) or metastatic NSCLC and has not been treated with systemic anticancer therapy for metastatic disease.
- Patient must have a documented RET-fusion
- Patient has measurable disease based on RECIST 1.1 as determined by the local site Investigator/radiology assessment.
- Patient has an ECOG PS of 0-1.
- Patient should not have received any prior anticancer therapy for metastatic disease.
* Patients can have received previous anticancer therapy (except a selective RET inhibitor) in the neoadjuvant or adjuvant setting but must have experienced an interval of at least ≥ 6 months from completion of therapy to recurrence.
* Patients that received previous immune checkpoint inhibitors in the adjuvant or consolidation following chemoradiation are not allowed to receive pembrolizumab if randomized in Arm B
- Patient is an appropriate candidate for and agrees to receive 1 of the Investigator choice platinum-based chemotherapy regimens if randomized to Arm B.
- Patient provides signed informed consent to participate in the study.

Critères de non-inclusion : Main exclusion criteria:
- Patient's tumor has any additional known primary driver alterations other than RET, such as targetable mutations of EGFR, ALK, ROS1, MET, and BRAF. Investigators should discuss enrollment with Sponsor designee regarding co-mutations.
- Patient previously received treatment with a selective RET inhibitor.
- Patient received radiotherapy or radiosurgery to any site within 14 days before randomization or more than 30 Gy of radiotherapy to the lung in the 6 months before randomization.
- Patient has a presence of Grade 2 or worse interstitial lung disease or interstitial pneumonitis, including radiation pneumonitis within 28 days before randomization.
- Patient has CNS metastases or a primary CNS tumor that is associated with progressive neurological symptoms or requires increasing doses of corticosteroids to control the CNS disease. If a patient requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks before Cycle 1 Day 1.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04222972
Promoteur :
Blueprint Medicines Corporation
Type de sponsor : Industriel
-
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Alexis Cortot

TEC / ARC / IDE :
Eric Wasielewski
eric.wasielewski@
chru-lille.fr
03.20.44.56.12

Statut de l'essai : OUVERT

MAJ : 28/10/2020