ABSTRACT: Interventions: Step1: Confirmation of dosage of each drug (Oxaliplatin and Irinotecan)
i)Induction treatment
The following drugs will be administered in 3week/cycle for 6cycles (maximum 8cycle, if investigator required). With regard to determination of oxaliplatin (OX) and Irinotecan (IRI) dosage, initial 3patients (pts) will be enrolled of level0. After finishing initial enrollment, Steering committee (SC) will evaluate safety of 3pts at the time of starting of cycle2 and will decide whether the proceeding same level (add 3 pts) or other level (level+1 or level-0.5). Final decision of Recommended Dose (RD) of OX and IRI will be required 6pts of safety evaluation in same level and will be endorsed by SC and Independent Data monitoring committee (IDMC).
1) Each drug dosage of CAPOXIRI+Bevacizumab
Bevacizumab (BEV: 7.5 mg/kg, i.v., 90, 60, 30 min, Day 1)
Irinotecan (IRI: 130 mg/m2, i.v., 90 min, Day 1)
Oxaliplatin (OX: 200 mg/m2, i.v., 120 min, Day 1)
Capecitabine (CAP: 800 mg/m2 p.o., twice daily, 14 days consecutively)
2) OX and IRI dose level
Level +1: IRI: 200 mg/m2, OX:130mg/m2
Level 0: IRI: 200 mg/m2, OX:100mg/m2
Level -0.5: IRI: 180 mg/m2, OX:100mg/m2
Level -1: IRI: 150 mg/m2, OX:100mg/m2
ii)Maintenance treatment
After finishing the induction treatment, investigator will select 1) 5-FU/LV+BEV (2weeks cycle) or 2) CAP+BEV treatment (3weeks/cycle).
1)5-FU/LV+BEV treatment
The following drugs will be administered in 2week/cycle until meeting discontinuation criteria.
- Each drug dosage of 5-FU/LV+BEV -
Bevacizumab (BEV: 5.0 mg/kg, i.v., 90, 60, 30 min, Day 1)
Leucovorin (LV: 200 mg/m2, i.v., 120 min, Day 1)
5-FU (3200 mg/m2, c.i.v., 48 hours, Day 1-3)
2)CAP+BEV treatment
The following drugs will be administered in 2week/cycle until meeting discontinuation criteria.
- Each
Primary outcome(s): Progression-free survival (PFS)
Study Design: randomized controlled trial, open(masking not used), active control, parallel assignment, treatment purpose
