This is an interventional, randomized open-label, parallel-group, multicenter, dose escalation phase Ib/II study, to investigate the combination of Regorafenib and XELOX as 2nd line treatment in mCRC patients.
This is a phase Ib/II trial, comprising Phase Ib and Phase II two parts. Phase Ib study is an open-label, single-arm, multicenter, dose escalation study of Regorafenib plus XELOX. In Phase Ib, max 15 patients(pts) could be enrolled based on the modified toxicity probability interval (mTPI) design. Phase II study is a randomized, open-label, parallel-group, multicenter study comparing Regorafenib + XELOX to XELOX alone. In phase II trial, a total of 39 patients will be recruited and randomized 2:1 into two groups, where 26 patients under Regorafenib + XELOX, and 13 patients under XELOX alone.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Phase Ib Group A: Regorafenib 120mg + XELOX; Group B: Regorafenib 160mg + XELOX; Group C: Regorafenib 80mg + XELOX.
Phase II: Regorafenib MAD qd po for 14 days, every 3 weeks.
Capecitabine 1000 mg/m2 bid po for 14 days.
The First Hospital of China Medical University
Shenyang, Liaoning, China
Maximum tolerated dose (MTD)
The MTD is defined as the highest dose that can be given so that toxicity probability is below the target toxicity PT=30%.
Time frame: 6 weeks
Progression-free survival (PFS)
PFS is defined as the time (days) from start of study treatment to date of first observed disease progression (investigator's radiological or clinical assessment) or death due to any cause, if death occurs before progression is documented.
Time frame: 1 year
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Safety and tolerability
Time frame: 3 years
Disease control rate (DCR)
o DCR is defined as the percentage of patients, whose overall best response was not progressive disease.
Time frame: 3 years
Overall response rate (ORR)
o ORR is defined as the percentage of patients with complete response (CR) or partial response (PR).
Time frame: 3 years
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Oxaliplatin 130mg/m2, day 1, every 3 weeks