Patologia: Tumori del colon retto
Osservazionale-Sperimentale: Sperimentale
Monocentrico-Multicentrico: Multicentrico
Randomizzato: Sì
Fase di studio: III
Linee di trattamento: Prima linea
Criteri di inclusione:
- Safety Lead-In = Male/female ≥ 18 years old
- Phase 3: Male/female ≥ 16 years old (where permitted locally)
- Histologically or cytologically confirmed Stage IV CRC that contains BRAF V600E mutation
- Prior systemic treatment in metastatic setting
- SLI: 0-1 regimens
- Phase 3: None
- Prior adjuvant or neoadjuvant therapy considered metastatic treatment if relapse/metastasis < 6 month from end of adj/neoadjuvant treatment
- Measurable disease (Phase 3)/ Measurable or evaluable disease (Safety Lead-in)
- ECOG PS 0-1
- Adequate organ function.
Criteri di esclusione:
- Tumors that are locally confirmed or unknown MSI-H or dMMR unless participant is ineligible to receive immune checkpoint inhibitors due to a pre-existing medical condition
- Active bacterial or viral infections in 2 weeks prior to starting dosing
- Symptomatic brain metastases.
Numero di pazienti previsti:
52 (in Italia)
Schema di trattamento:
Safety Lead-In (SLI) - Cohort 1
Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
Safety Lead-In (SLI) - Cohort 2
Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
Phase 3 Arm A
Encorafenib (300 mg QD) + cetuximab 500 mg/m2 (120-minute IV infusion Q2W).
Phase 3 Arm B
Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks -OR- Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
Phase 3 Arm C (control Arm)
Every two weeks: Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Every two weeks: Irinotecan 165 mg/m2 (90-minute IV infusion) Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 2400 or 3200 mg/m2 continuous IV infusion over 46 48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Every two weeks: Irinotecan 180 mg/m2 (90-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Oxaliplatin 130 mg/m2 (120-minute IV infusion) every 3 weeks Capecitabine 1000 mg/m2 oral tablet twice daily on Days 1-14 Bevacizumab (optional; given per prescribing instructions)
Trattamento sperimentale:
Safety Lead-in:
- Encorafenib + cetuximab + FOLFIRI
- Encorafenib + cetuximab + mFOLFOX6
Phase III:
Arm A: Encorafenib + cetuximab
Arm B: Encorafenib + cetuximab + mFOLFOX6
oppure
Encorafenib + cetuximab + FOLFIRI
Trattamento di controllo:
Phase III:
- mFOLFOX6 ± bevacizumab
- FOLFIRI ± bevacizumab
- FOLFOXIRI ± bevacizumab or
- CAPOX ± bevacizumab.
Obiettivi primari dello studio:
The purpose of the study is to evaluate whether encorafenib plus cetuximab (EC), alone or in combination with chemotherapy, can improve clinical outcomes relative to current standard of-care chemotherapy in participants with previously untreated BRAF V600E-mutant mCRC. Since encorafenib has not previously been combined with chemotherapy, the tolerability and PK of EC in combination with mFOLFOX6 and in combination with FOLFIRI will be evaluated in separate cohorts in the safety lead-in portion of the trial in order to identify which chemotherapy combination is to be used in the Phase 3 portion of the study.
Data di inizio dell'arruolamento: 06.01.2021
Data di fine dell'arruolamento: 22.01.2024
Fondazione Poliambulanza Istituto Ospedaliero
Via Bissolati 57 - 25124 Brescia - BS
Riferimento: Dr. Alberto Zaniboni
Telefono: 0303518503
Email: alberto.zaniboni@poliambulanza.it
Grande Ospedale Metropolitano Niguarda
Piazza Ospedale Maggiore 3 - 20162 Milano - MI
Oncologia Falck
Istituto Europeo di Oncologia
Via Ripamonti 435 - 20141 Milano - MI
Divisione di Oncologia Medica Gastrointestinale
Riferimento: Dr.ssa Maria Giulia Zampino
Email: maria.zampino@ieo.it
A.O.U. Policlinico di Modena
Via del Pozzo 71 - 41100 Modena - MO
Riferimento: Dr. Fabio Gelsomino
Telefono: 0594224982
Email: gelsomino.fabio@aou.mo.it
Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD
UOC Oncologia Medica 1
Riferimento: Dr.ssa Sara Lonardi
Telefono: 0498215910
Email: sara.lonardi@iov.veneto.it
AUSL/IRCCS di Reggio Emilia
Viale Risorgimento 80 - 42123 Reggio nell'Emilia - RE
Riferimento: Dr. Carmine Pinto
Telefono: 0522296614
Email: carmine.pinto@ausl.re.it
IRCCS Candiolo (TO)
St.Provinciale Km 3,95 SP142 - 10060 Candiolo - TO
Riferimento: Dr.ssa Elisabetta Fenocchio
Telefono: 0119933250
Email: elisabetta.fenocchio@ircc.it
A.O.U San Luigi Gonzaga
Regione Gonzole 10 - 10043 Orbassano - TO
SCDU Oncologia Medica
Riferimento: Prof. Giorgio Vittorio Scagliotti
Telefono: 0119026414
Email: giorgio.scagliotti@unito.it
AOU di Cagliari - Presidio Policlinico Monserrato
St.Statale 554, Km 4500 - 09100 Monserrato - CA
Policlinico Universitario Duilio Casula
Riferimento: Prof. Mario Scartozzi
Telefono: 07051096107
Email: sperimentazioniclinicheunica@gmail.com
IRCCS Ospedale Casa Sollievo della Sofferenza
Viale Cappuccini 1 - 71013 San Giovanni Rotondo - FG
Riferimento: Dr. Evaristo Maiello
Telefono: 0882410640
Email: e.maiello@operapadrepio.it
AOU degli studi della Campania Luigi Vanvitelli
Piazza Luigi Miraglia 2 - 80138 Napoli - NA
UOC Oncoematologia, via Pansini
Riferimento: Dr.ssa Erika Martinelli
Telefono: 0815666729
Email: erika.martinelli@unicampania.it
Numero di iscrizione a registro: 2020-001288-99
Data di inserimento: 23.02.2022
Data di aggiornamento: 19.01.2023
Pfizer
PPD
Istituto Oncologico Veneto IRCCS, Padova
Riferimento: Dr.ssa Sara Lonardi
Telefono: 0498215910
Email: sara.lonardi@iov.veneto.it
Localita: Padova