Unresectable/Metastatic Colorectal Cancer
Conditions
Keywords
Fruquintinib, Camrelizumab, Capecitabine, mCRC, salvage therapy
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.
Interventions
DRUGFruquintinib 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
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Metastatic or locally advanced, unresectable colorectal cancer confirmed by histology or cytology 2. 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 3. 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. 4. Target lesion defined by the Response Evaluation Criteria in Solid Tumor (RECIST criteria) 5. Age ≥18 years old, performance status (ECOG) score ≤ 2 6. Estimated expectancy life at least 12 weeks 7. Adequate blood, liver and kidney function, as follows: 1. Hemoglobin ≥8g/dl, 2. neutrophil absolute count ≥1000/μL, 3. platelets ≥ 75,000 /μL; 4. Total bilirubin ≤1.5 x upper limit of normal (ULN), 5. alkaline phosphatase, aspartate aminotransferase (AST (SGOT) and alanine aminotransferase (ALT (SGPT)) ≤2.5 x ULN (if liver metastasis is present, ≤5 x ULN), 6. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance \>50mL/min (calculated according to Cockcroft Gault formula), 7. urinary protein excretion (if protein \>30 mg/dL or 2+, 24-hour urinary protein quantity must ≤1g) 8. 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) 9. 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 10. Consent to provide blood samples for specific relevant analyses 11. Have the ability to understand and sign the written informed consent
Exclusion criteria
1. 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 2. Untreated or symptomatic brain metastases 3. The
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | Progression-free survival is defined as the time from study enrollment to first disease progression or death, whichever occurs first |
| Overall survival | from the date of enrollment to the date of death from any cause，assessed up to 2 years | 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 | from the date of the first medicine to 28days after the last medicine，assessed up to 2 years | 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 | from the date of enrollment to the date of progression，assessed up to 2 years | Explore the correlation between dynamics of serum ctDNA and efficacy. |
Countries
China
Contacts
Primary ContactQiong Yang, Doctor
Backup Contactkaicong zhang, master
Outcome results
None listed