FOLFOXIRI-based regimen is more used as a first-line therapeutic approach for patients diagnosed with unresectable or metastatic colorectal cancer for its superior efficacy. However, there are no standard recommendations for second-line therapy after progression on FOLFOXIRI with or without targeted therapy. Here, the investigators conduct this open-label, single arm phase II study to evaluate whether fruquintinib in combination with camrelizumab and capecitabine can be the salvage therapy following FOLFOXIRI based regimen for mCRC. Patients diagnosed with unresectable or metastatic colorectal cancer progression on FOLFOXIRI-based regimen are included;or patients have progression or untolerated toxicity with irinotecan, oxaliplatin and fluorouracil successively within one year; patients with BRAF mutation were allowed to receive BRAF inhibitor therapy with or without MEK inhibitor therapy after FOLFOXIRI-based regimen.
Patients participated in this study will receive fruquintinib 5 mg once daily, 2 weeks on/1 week off, plus camrelizumab 200 mg Q3W and capecitabine 750mg/square meter twice, 2 weeks on/1 week off, repeated every three weeks. The primary endpoint is Objective Response Rate(ORR). The investigators estimated that 30 patients were necessary. Secondary endpoints include progression-free survival, overall survival, safety, and exploratory ctDNA for efficacy prediction for unresectable or metastatic colorectal cancer.
Metastatic or locally advanced, unresectable colorectal cancer confirmed by histology or cytology
The occurrence of metastases after radical resection of colorectal cancer does not require additional histological or cytological confirmation unless more than 5 years since surgery for the primary tumor
Progression or toxicity intolerance of first-line treatment with or without targeted drugs (bevacizumab or cetuximab) with FOLFOXIRI regimen or the sequential administration of irinotecan, oxaliplatin, and fluorouracil within a year; if patients with BRAF mutations, who have been treated with BRAF inhibitor alone or in combination with MEK inhibitor also can be included.
Target lesion defined by the Response Evaluation Criteria in Solid Tumor (RECIST criteria)
Received antitumor chemotherapy or biotherapy within 28 days prior to the first use of the investigational drug. The exception is a single dose of radiotherapy up to 8Gy for pain relief of non-target lesion during the first 14 days of enrollment
Untreated or symptomatic brain metastases
History of heart disease: Congestive heart failure (CHF) grade II or higher, according to the New York Heart Association (NYHA); Active coronary artery disease and myocardial infarction within 6 months prior to study initiation; New angina or unstable angina (occurrence at rest) that have not been evaluated within 3 months; arrhythmias that require antiarrhythmic therapy; except in participants who have been treated and who the investigator believes have stable/controlled disease;
Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg) and a history of hypertensive crisis or hypertensive encephalopathy;
Single group
Fruquintinib plus camrelizumab and capecitabine
Drugfruquintinib 5 mg once daily, 2 weeks on/1 week off, plus camrelizumab 200 mg Q3W and capecitabine 750mg/square meter twice, 2 weeks on/1 week off, q3w
Objective Response Rate
Objective Response Rate is defined as the percentage of patients relative to the total of enrolled subjects who achieve a complete response (CR) or partial response (PR) based on CT or MRI scan images confirmed 4-6weeks later.
Progression-free survival
Progression-free survival is defined as the time from study enrollment to first disease progression or death, whichever occurs first
Overall survival
Overall survival is defined as the time from study enrollment to the date of death due to any cause
Adverse Events and Serious Adverse Events
Assessment of Safety and tolerance for Fruquintinib plus camrelizumab and capecitabine as salvage therapy in patients with unresectable/metastatic colorectal cancer，including incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTCAE Version 5.0.
Circulating tumor DNA(ctDNA) and efficacy
Explore the correlation between dynamics of serum ctDNA and efficacy.
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