TRIBE-2: a phase III, randomized, open-label, strategy trial in unresectable metastatic colorectal cancer patients by the GONO group

BMC Cancer

Study Protocol

Luca Boni¹  Chiara Valsuani²  Samantha Di Donato³  Alessandro Passardi⁴  Giuseppe Aprile⁵  Alfredo Falcone⁶  Carlotta Antoniotti⁶  Gianluca Masi⁶  Federica Marmorino⁶  Chiara Cremolini⁶  Lisa Salvatore⁶  Marta Schirripa⁶  Fotios Loupakis⁶  Filippo Pietrantonio⁷  Vittorina Zagonel⁸  Sara Lonardi⁸  Vincenzo Ricci⁹  Giacomo Allegrini^1,10  Daniele Santini^1,11  Emiliano Tamburini^1,12  Monica Ronzoni^1,13  Gianluca Tomasello^1,14 

[1] Centro per il Coordinamento per le Sperimentazioni Cliniche, Istituto Toscano Tumori, AOU Careggi, viale Pieraccini 6, 50139, Florence, Italy;Dipartimento Oncologico, A.S.L. 1 Carrara, P.zza Sacco e Vanzetti, 2, 54033, Carrara, Italy;Dipartimento Oncologico, AUSL 4 Prato, Via Mazzamuti 7, 59100, Prato, Italy;Dipartimento di Oncologia Medica, IRCCS-IRST (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori), via Piero Maroncelli 40, 47014, Meldola, FC, Italy;Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Piazzale Santa Maria della Misericordia 15, 33100, Udine, Italy;Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Oncologia Medica 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126, Pisa, Italy;Fondazione I.R.C.C.S, Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy;Oncologia Medica 1, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), via Gattamelata 64, 35128, Padua, Italy;Oncologia Medica, Dipartimento di Oncologia Clinica, Azienda Sanitaria Ospedaliera S. Croce, Via Michele Coppino 26, 12100, Cuneo, Italy;Oncologia Medica, Ospedale Felice Lotti, via Roma 147, 56025, Pontedera, Italy;Oncologia Medica, Università Campus Bio-Medico, vai Alvaro del Portillo 200, 00128, Rome, Italy;Ospedale Infermi, Via Coriano 38, 47924, Rimini, Italy;Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy;SC Oncologia, Istituti Ospedalieri Di Cremona, Viale Concordia 1, 26100, Cremona, Italy;

关键词: Colorectal cancer;    Bevacizumab;    Strategy;    Folfoxiri;    Clinical trial;   

DOI  :  10.1186/s12885-017-3360-z

 received in 2015-11-24, accepted in 2017-05-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundChemotherapy plus bevacizumab is a standard first-line treatment for unresectable metastatic colorectal cancer patients. Different chemotherapy backbones may be chosen, including one to three drugs, based on patients’ general conditions and comorbidities, treatments’ objectives, and disease characteristics. TRIBE trial demonstrated a significant advantage in terms of progression-free survival and overall survival for FOLFOXIRI plus bevacizumab as compared with FOLFIRI plus bevacizumab. Based on recent evidence, the de-intensification of the upfront regimen after 4–6 months of treatment is nowadays regarded as a valuable option. Moreover, the prolonged inhibition of angiogenesis, and in particular the continuation of bevacizumab beyond the evidence of disease progression, is an efficacious strategy in the treatment of metastatic colorectal cancer patients.Methods/designTRIBE-2 is a prospective, open-label, multicentric phase III randomized trial in which unresectable and previously untreated metastatic colorectal cancer patients are randomized to receive first-line FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab after disease progression or FOLFOXIRI plus bevacizumab followed by the re-introduction of the same regimen after disease progression. The primary endpoint is to compare the efficacy of the two proposed treatment strategies in terms of Progression Free Survival 2.DiscussionThe TRIBE-2 study aims at answering the question whether the upfront use of FOLFOXIRI improves the clinical outcome of metastatic colorectal cancer patients, when compared with the pre-planned, sequential use of oxaliplatin-based and irinotecan-based doublets. Both proposed treatment strategies are designed to exploit the effectiveness of the prolonged inhibition of angiogenesis, alternating short (up to 4 months) induction periods and less intensive maintenance phases.Trial registrationTRIBE2 is registered at Clinicaltrials.gov: NCT02339116. January 12, 2015. TRIBE-2 is registered at EUDRACT 2014–004436-19, October 10, 2014.

【 授权许可】

CC BY   
© The Author(s). 2017