Fruquintinib Plus Camrelizumab and Capecitabine as Salvage Therapy After Progression on FOLFOXIRI-based First-line Treatment in Patients With Unresectable/Metastatic Colorectal Cancer: a Prospective Phase II Study
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)
• Age ≥18 years old, performance status (ECOG) score ≤ 2
• Estimated expectancy life at least 12 weeks
• Adequate blood, liver and kidney function, as follows:
∙ Hemoglobin ≥8g/dl,
‣ neutrophil absolute count ≥1000/μL,
‣ platelets ≥ 75,000 /μL;
‣ Total bilirubin ≤1.5 x upper limit of normal (ULN),
‣ alkaline phosphatase, aspartate aminotransferase (AST (SGOT) and alanine aminotransferase (ALT (SGPT)) ≤2.5 x ULN (if liver metastasis is present, ≤5 x ULN),
‣ Serum creatinine ≤1.5 x ULN or calculated creatinine clearance \>50mL/min (calculated according to Cockcroft Gault formula),
‣ urinary protein excretion (if protein \>30 mg/dL or 2+, 24-hour urinary protein quantity must ≤1g)
• International Normalized Ratio (INR) or activated partial thromboplastin time (APTT) \<1.5 x ULN (thromboembolic event must be ruled out if D-dimer is abnormal)
• Negative pregnancy test within 7 days before enrollment; Pregnancy tests can only be omitted in women who do not have any reproductive potential (e.g., postmenopausal women who had amenorrhea ≥2 years or prior hysterectomy or bilateral oophorectomy). Fertile wo-men and men must consent to the use of appropriate contraception at the time of enrollment and during study participation. If a woman becomes pregnant or suspects that she is pregnant while participating in this study, she must notify her physician immediately; Breastfeeding women must be excluded
⁃ Consent to provide blood samples for specific relevant analyses
⁃ Have the ability to understand and sign the written informed consent