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
Overview
- Phase
- Phase 2
- Intervention
- Fruquintinib plus camrelizumab and capecitabine
- Conditions
- Unresectable/Metastatic Colorectal Cancer
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Objective Response Rate
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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;
Exclusion 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
- •The exclusion criteria of fruquintinib are as follows:
- •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;
- •History of arterial thrombosis or embolism events (within 6 months)
- •Critical vascular diseases (such as aortic aneurysm, aortic dissection, symptomatic peripheral vascular disease)
- •People with bleeding tendency or coagulation disorder
- •Had major surgery (including open biopsy, severe trauma, etc.) within 14 days prior to study enrollment, or expected to require major surgery during the study period, and had minor surgery (excluding Implantable Venous Access Port or peripherally inserted central venous catheter) within 7 days prior to study enrollment
- •Abdominal fistula, gastrointestinal perforation, peptic ulcer or abdominal abscess in the past 6 months
Arms & Interventions
Fruquintinib plus camrelizumab and capecitabine
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, q3w
Intervention: Fruquintinib plus camrelizumab and capecitabine
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: Undergo imaging examination to evaluate efficacy every 6 weeks ±7 days, and every 9 weeks ±7 days in the second year (up to 2 years)
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.
Secondary Outcomes
- Overall survival(from the date of enrollment to the date of death from any cause，assessed up to 2 years)
- Circulating tumor DNA(ctDNA) and efficacy(from the date of enrollment to the date of progression，assessed up to 2 years)
- Progression-free survival(Undergo imaging examination to evaluate efficacy every 6 weeks ±7 days, and every 9 weeks ±7 days in the second year (up to 2 years))
- Adverse Events and Serious Adverse Events(from the date of the first medicine to 28days after the last medicine，assessed up to 2 years)