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Randomized phase II study of FOLFIRI plus ramucirumab versus FOLFOXIRI plus ramucirumab as first-line treatment in patients with metastatic colorectal cancer (WJOG9216G) (WJOG9216G, RECAST)

Randomized phase II study of FOLFIRI plus ramucirumab versus FOLFOXIRI plus ramucirumab as first-line treatment in patients with metastatic colorectal cancer (WJOG9216G) (WJOG9216G, RECAST)

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The baseline characteristics in arm A (FOLFIRI + ramucirumab) and arm B (FOLFORIXI + ramucirumab) were as follows: median age, 64 and 65; male, 66% and 70%; right colon, 29% and 30%; RAS mutant, 61% and 67%; BRAF mutant, 9% and 3%; liver-limited disease, 32% and 19%, respectively.

This is a randomized phase II study comparing FOLFIRI + ramucirumab and FOLFORIXI + ramucirumab. One patient in arm B did not receive the study treatment due to progression on duodenal stenosis. At the cut-off date of final analysis (2/Mar/2023), all patients in arm A and 61 patients in arm B had discontinued the protocol treatment.

Major grade 3 or higher adverse events (incidence in arm A/B) were neutropenia (44.1/72.6%), hypertension (15.3/19.4%), proteinuria (13.6/12.9%), anorexia (3.4/14.5%), febrile neutropenia (3.4/11.3%), and diarrhea (1.7/8.1%). Two treatment-related death was observed in arm B due to pulmonary infection and colonic perforation. Serious adverse events which required or extended admissions were observed in 11 cases in arm A and 36 cases in arm B.

The overall response rate (ORR) as primary endpoint was 57.6% in arm A vs. 60.3% in arm B (odds ratio 1.11, p=0.76). As secondary endpoints, median progression-free survival (PFS) was 11.7 vs. 10.5 months (hazard ratio 1.13) with median follow-up of 27.4 vs. 25.3 months, and early tumor shrinkage rate at week 8 was 71.2 vs. 52.4%, respectively (p = 0.03).

FOLFOXIRI plus ramucirumab was not superior to FOLFIRI plus ramucirumab for ORR and PFS in first-line treatment for metastatic colorectal cancer. The safety of FOLFOXIRI plus ramucirumab and FOLFIRI plus ramucirumab were comparable with those previously reported in FOLFOXIRI plus bevacizumab and FOLFIRI plus bevacizumab, respectively.

Sept. 01, 2024

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs041180166

Kito Yosuke

Ishikawa Prefectural Central Hospital

2-1 Kuratsuki-higashi, Kanazawa,Ishikawa 920-8530 , Japan

kitoyo9100@gmail.com

Kito Yosuke

Ishikawa Prefectural Central Hospital

2-1 Kuratsuki-higashi, Kanazawa,Ishikawa 920-8530 , Japan

+81-76-237-8211

kitoyo9100@gmail.com

Complete

June. 01, 2017

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1) Histologically or cytologically diagnosed adenocarcinoma of the colon or rectum (excluding the appendix and anal canal).
2) Tumor is clinically determined to be unresectable for a radical cure.
3) Age of 20-75 years.
4) ECOG PS of 0-1 (a PS 0 is required for subjects aged 71-75 years).
5) Measurable lesion according to RECIST, version 1.1.
6) No history of chemotherapy (however, subjects may register if they have received adjuvant chemotherapy with fluoropyrimidine monotherapy and the cancer recurrence occurred > 24 weeks after the last dose. Patients who have received OX-based adjuvant chemotherapy may not register.)
7. Retained organ function.
8. UGT1A1 gene status of wild type (*1/*1), or *28, *6 genetic polymorphism single hetero-type (*1/*28, *1/*6).
9. The RAS mutation status (wild-type, mutant or not definable) of the patients is known prior to randomization.

1) Serious complications.
2) Receipt of a blood transfusion or hematopoietic factor therapy within 2 weeks prior to registration.
3) Grade 2 or worse peripheral sensory neuropathy.
4) History of Grade 3 or worse thromboembolism within 6 months before the scheduled treatment start date.
5) Receiving anti-platelet agents. Aspirin use at doses up to 325 mg/day is permitted.
6) Women who are pregnant, breastfeeding, had a positive pregnancy test, or women and men who do not wish to use contraception.

Both

First-line treatment in patients with metastatic colorectal cancer

Arm A: FOLFIRI plus ramucirumab (Rmab) treatment
- Rmab: 8 mg/kg/day1
- l-leucovorin (l-LV): 200 mg/m2/day1
- irinotecan (IRI): 180 mg/m2/day1
- bolus 5-FU: 400 mg/m2/day1
- infusional 5-FU: 2400 mg/m2/day1-3
Every 2 weeks

Arm B: FOLFOXIRI plus Rmab treatment
Induction therapy: 8 courses (maximum of 12 courses)
- Rmab: 8 mg/kg/day1
- IRI: 165 mg/m2/day1
- l-LV: 200 mg/m2/day1
- oxaliplatin (OX): 85 mg/m2/day1
- infusional 5-FU: 3200 mg/m2/day1-3
Every 2 weeks

Maintenance therapy: 5-FU/l-LV+Rmab, every 2 weeks

Objective response rate

Overall survival, progression-free survival, time to treatment failure, time to second progression or death, early tumor shrinkage, depth of response, R0 resection rate, and safety

+81-55-989-5222

Jan. 15, 2019

none