MONARCC: a randomised phase II study of panitumumab monotherapy and panitumumab plus 5-fluorouracil as first-line therapy for RAS and BRAF wildtype metastatic colorectal cancer: a study by the Australasian Gastrointestinal Trials Group (AGITG)

BMC Cancer

Niall Tebbutt¹  Jeff Cuff²  Christopher Steer³  Karen Briscoe⁴  Chris Karapetis⁵  Susan Caird⁶  Eva Segelov⁷  Lisa Bailey⁸  Sonia Yip⁸  Kate Wilson⁸  David Espinoza⁸  Katrin Sjoquist⁸  Ho Wai Derrick Siu⁹  Jennifer Shannon^1,10  Nick Pavlakis^1,11  Rahul Ladwa^1,12  Matthew Burge^1,13  Melanie Wuttke^1,14  Lorraine Chantrill^1,15  Subotheni Thavaneswaran^1,16  Alessandra Francesconi^1,17  Jeannie Tie^1,18  Timothy Price^1,19  Ratnesh Srivastav^2,20 

[1] Austin Hospital, Melbourne, Australia;Australasian Gastrointestinal Group (AGITG), Sydney, Australia;Border Medical Oncology Research Unit, Albury-Wodonga, Australia;Coffs Harbour Health Campus, Coffs Harbour, Australia;Flinders Medical Centre, Adelaide, Australia;Gold Coast University Hospital, Gold Coast, Australia;Monash Medical Centre, Melbourne, Australia;NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia;NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia;Camperdown, Australia;Nepean Hospital, Sydney, Australia;Northern Cancer Institute, Sydney, Australia;Princess Alexandra Hospital, Brisbane, Australia;Royal Brisbane and Women’s Hospital, Brisbane, Australia;The Prince Charles Hospital, Brisbane, Australia;Royal Hobart Hospital, Hobart, Australia;Shoalhaven Cancer Care Centre, Nowra, Australia;St Vincent’s Public Hospital, Sydney, Australia;Sunshine Coast University Hospital, Sunshine Coast, Australia;Sunshine Hospital, Melbourne, Australia;The Queen Elizabeth Hospital, Adelaide, Australia;The Tweed Hospital, Tweed Heads, Australia;

关键词: Metastatic colorectal cancer;    Elderly;    Older adults;    RAS;    BRAF;    Panitumumab;    Cetuximab;    Clinical trial;   

DOI  :  10.1186/s12885-021-08644-4

来源: Springer

【 摘 要 】

BackgroundDoublet chemotherapy in combination with a biologic agent has been a standard of care in patients with metastatic colorectal cancer for over a decade. The evidence for a “lighter” treatment approach is limited to mono-chemotherapy plus bevacizumab in the RAS unselected population. Anti-EGFR antibodies have activity as monotherapy or in combination with chemotherapy in RAS wildtype metastatic colorectal cancer; however their role in first-line treatment in combination with 5-fluorouracil monotherapy or when given alone has not been well studied. MONARCC aims to investigate this approach in an elderly population.Methods/designMONARCC is a prospective, open-label, multicentre, non-comparative randomised phase II trial. Eligible patients aged ≥70 with unresectable metastatic, untreated, RAS/BRAF wildtype metastatic colorectal cancer will be randomised 1:1 to receive panitumumab alone or panitumumab plus infusional 5-fluorouracil. RAS and BRAF analyses will be performed in local laboratories. Comprehensive Health Assessment and Limited Health Assessments will be performed at baseline and at 16 weeks, respectively, to assess frailty. The Patient Symptom Questionnaire and Overall Treatment Utility are to be undertaken at different timepoints to assess the impact of treatment-related toxicities and quality of life. Treatment will be delivered every 2 weeks until disease progression, unacceptable toxicity (as determined by treating clinician or patient), delay of treatment of more than 6 weeks, or withdrawal of consent. The primary end point is 6-month progression-free survival in both arms. Secondary end points include overall survival, time to treatment failure, objective tumour response rate as defined by RECIST v1.1 and safety (adverse events). Tertiary and correlative endpoints include the feasibility and utility of a comprehensive geriatric assessment, quality of life and biological substudies.DiscussionMONARCC investigates the activity and tolerability of first-line panitumumab-based treatments with a view to expand on current treatment options while maximising progression-free and overall survival and quality of life in molecularly selected elderly patients with metastatic colorectal cancer.Trial registrationAustralia New Zealand Clinical Trials Registry: ACTRN12618000233224, prospectively registered 14 February 2018.

【 授权许可】

CC BY