The aim of this study is to evaluate the efficacy and safety of short course radiotherapy followed by fruquintinib combined with Sintilimab as the first-line treatment of advanced mCRC compared to bevacizumab combined with capecitabine in patients unfit for intensive therapy.
Anti-angiogenic therapy combined with immune checkpoint inhibitors in advanced mCRC has shown promising efficacy with acceptable toxicities. Radiotherapy may reshape the tumor immune microenvironment, thereby improving the efficacy of subsequent anti angiogenic drugs combined with immunotherapy. The study is a prospective, multi-centered, two-stage clinical study with 220 unresectable advanced mCRC patients unfit for oxaliplatin or irinotecan-based intensive chemotherapy enrolled. In phase 1b, 20 patients will be recruited and the efficacy and safety of SCRT followed by fruquintinib plus sintilimab will be explored. In phase 2, 200 patients will be randomized and the efficacy and safety will be compared between SCRT followed by fruquintinib plus sintilimab and capecitabine plus bevacizumab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
SCRT: 5\*5Gy for 5 days, after a one-week rest, with fruquintinib plus sintilimab followed; Fruquintinib: qd po, 4mg/d, 2weeks on/1 week off, q3w; Sintilimab: intravenous infusion, 200mg, on day 1, q3w.
Capecitabine: bid po, 1000mg/m², on days 1-14, q3w; Bevacizumab: intravenous infusion, 7.5mg/kg, on day 1, q3w.
Ji Zhu
Hangzhou, Zhejiang, China
Phase 1b - Objective Response Rate (ORR)
ORR according to RECIST v1.1, as assessed by the Investigator
Time frame: From randomization until disease progression (up to approximately 3-5 years)
Phase 2 - Progression-free Survival (PFS)
PFS according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the Investigator
Time frame: From randomization until disease progression (up to approximately 3-5 years)
Tolerability and safety of study regimens
Number of Participants With Treatment-emergent Adverse Events (TEAEs) according to CTCAE v5.0
Time frame: From randomization until the end of treatment (up to approximately 3-5 years)
Disease Control Rate (DCR)
DCR according to RECIST v1.1, as assessed by the Investigator
Time frame: From randomization until disease progression (up to approximately 3-5 years)
Overall Survival OS)
OS according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the Investigator
Time frame: From randomization until disease progression (up to approximately 3-5 years)
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