Table 4.
Study assessments
| Procedures | Screening (−28 days) |
Cycle 1,3,5,7a (+ 3 days) |
Cycle 2,4,6,8 a (+ 3 days) |
Maintenance a (+ 3 days) |
End of treatment a | Post-treatment Follow up a |
|---|---|---|---|---|---|---|
| Signed informed consent | X | |||||
| Medical history and baseline conditions | X | |||||
| Physical examination | X | X | X | X | X | |
| Parametersb | X | X | X | X | X | |
|
Hematology and serum chemistryc |
X | X | X | X | X | |
| Protein dipstick | X | X | X | X | X | |
| Adverse Events | X | X | X | X | X | |
| Radiological assessmente, CEAc | X | X | X | X | ||
| QLQ-C30 questionnairef | X | X | X | X | ||
| Blood sampleg | X | X | ||||
| FOLFOXIRI administration | X | X | ||||
| Nivolumab and Bevacizumab administration | X | X | X | |||
| Survival follow-up | X |
aEach cycle is 14 days. Study drugs administration occurs on day1 (+/− 3 days) of each cycle. All clinical and laboratory assessments must occur within 3 days prior the administration. The end of treatment should occur within 30 days after last dose of study treatment. The post-treatment follow-up visit occur every 3 months (+/− 14 days) for 3 years
bVital signs will include: weight, respiratory rate, pulse rate, temperature and systolic and diastolic blood pressure. At baseline height and BSA
cHematology analysis (within 7 days before Cycle 1) consist of: hemoglobin, WBC and platelet count, BUN, creatinine, glucose, total bilirubin, sodium, potassium, calcium, AST, ALT, alkaline phosphatase, LDH, albumin. CEA will be tested every 8 weeks with radiological assessment. Amylase, lipase, TSH, FT3, FT4, will be done on cycle 2,4,6,8
dIf proteinuria is 2+, should undergo a 24-h urine collection and must demonstrate 1 g of protein/24 h
eRadiological assessment will be performed within 28 days prior to start of study treatment and every 8 weeks (± 1 week), regardless cycle of treatment; in details, during chemotherapy phase prior to cycle 5, at the end of chemotherapy (cycle 8)
fQLQ-C30 will be completed at baseline, at cycles 4 and 8 of chemotherapy phase, every 4 cycles thereafter and at end of treatment visit
gBlood sample will be collected at baseline, prior to cycle 5, at the end of chemotherapy and at time of progression