Pancreatic cancer represents the most lethal of the common malignancies with a 5-year survival rate of less than 5%. For patients who are eligible for potentially curative resection, despite mortality and morbidity rates after surgery have improved, the recurrence rate is up to 85% within 2 years. FOLFIRINOX (fluoropyrimidine/leucovorin plus irinotecan and oxaliplatin) has been proved to significantly improve the prognosis and is recommended as first line treatment in patients with advanced pancreatic cancer. However, the regimen is limited due to the severe adverse effects. Thus, the investigators replaced 5-FU and leucovorin in the FOLFIRINOX regimen with oral S-1, a new oral fluoropyrimidine derivative which was proved to be the well-tolerated and effectively in large III phase randomized clinical trial, to form the SIRIOX regimen. A phase I clinical trial from Japan found that SOXIRI (S-1, oxaliplatin and irinotecan) works in patients with advanced pancreatic cancer. In this study, the researchers intend to investigate the activity and safety of the combination of this regimen in patients with advanced pancreatic cancer, as first- or second-line chemotherapy.
Pancreatic cancer (mainly pancreatic ductal adenocarcinoma, PDAC) is a disease with extremely poor prognosis, and is often fatal. Surgical resection is the only potentially curative technique for management of PDAC, but only approximately 15% to 20% of patients are candidates for pancreatectomy at the time of diagnosis Gemcitabine (Gem) is widely used as a standard chemotherapeutic agent for advanced pancreatic cancer. FOLFIRINOX (fluoropyrimidine/leucovorin plus irinotecan and oxaliplatin), compared with Gem, has been proved to significantly improve the objective response rate (31.6% VS. 9.4%, P \< 0.001) and prolong the median survival time (11.1 months VS. 6.8 months, P \< 0.001) for patients with metastatic pancreatic ductal adenocarcinoma(PDAC), who had a performance status of ECOG 0-1 score. However, it is undeniable that the adverse effects of FOLFIRINOX are severe. For example, the incidence of 3/4 grade neutrophil decrease in patients receiving FOLFIRINOX is significantly higher than those with Gem (45.7% VS. 21%, P \< 0.001). Thus, it is difficult for many patients to receive standard FOLFIRINOX and benefit from the protocol. Therefore, the investigators aim to explore an improvement program of FOLFIRINOX, hoping to better benefit patients. S-1 is a new oral fluoropyrimidine derivative in which tegafur is combined with two 5-chloro-2, 4-dihydroxypyridine modulators and oteracil potassium, a potentiator of 5-fluorouracil's (5-FU's) antitumor activity that also decreases gastrointestinal toxicity. Combination chemotherapy with Gem and S-1 is reportedly well tolerated and benefits patients with advanced PDAC. Based on the results of the GEST study, S-1 is found to be non-inferior to Gem in patients' survival. Therefore, in this study, the investigators replaced 5-FU and leucovorin in the FOLFIRINOX regimen with oral S-1, forming a SIRIOX regimen to treat patients with advanced pancreatic cancer, as first- or second-line chemotherapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
65
Patients are planned to receive the SIRIOX regimen including S-1 (BSA \< 1.2m2, 40 mg/day; BSA = 1.2\~1.4 m2, 60 mg/day; BSA = 1.4\~1.6 m2, 80 mg/day; BSA \> 1.6 m2, 100 mg/day; oral twice daily on days 1-7, days 15-21)of every cycle. • 28 days a cycle.
Patients are planned to receive the SIRIOX regimen including Oxaliplatin (OXA, 85 mg/m2; d1,d15) of every cycle. • 28 days a cycle
Patients are planned to receive the SIRIOX regimen including Irinotecan (IRI, 180mg/m2; day 1,day 15) of every cycle. • 28 days a cycle
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
Shanghai, Shanghai Municipality, China
RECRUITINGDepartment of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University; 270 Dong An Road, Shanghai 200032, China
Shanghai, China
RECRUITINGprogression free survival (PFS)
The time from the beginning of randomization to the earliest date of confirmation of tumor progression or the patient death for any reason. If the above criteria are not reached, the date of the last evaluation will be used.
Time frame: 6 weeks (1.5 cycle)
objective response rate (ORR)
The proportion of patients whose tumors shrink to a certain amount for a certain period of time and include cases of complete response (CR) and partial response (PR). Calculated as: (CR cases + PR cases) / FAS × 100 (%); FAS (full analysis set) refers to the case of qualified patients, administered more than one case. Tumor remission rates are calculated according to the RECIST guidelines (version 1.1)
Time frame: 6 weeks (1.5 cycle)
overall survival (OS)
The time from the beginning of randomization to the earliest date of confirmation of the patient death for any reason.
Time frame: through study completion, an average of 18 months
Toxicity evaluated according to the Common Terminology Criteria Adverse Events
Toxicity is evaluated according to the Common Terminology Criteria Adverse Events Version3.0,CTCAEv3.0
Time frame: every week
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