NCT03403101

The Combination Chemotherapy of SIRIOX as First- or Second-Line Chemotherapy for Pancreatic Cancer

A Phase II, Single Arm, Open Label Study to Evaluate the Efficacy and Safety of the Combination of S-1, Irinotecan and Oxaliplatin (SIRIOX) in Treating Patients With Advanced Inoperable or Metastatic Pancreatic Cancer

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 65 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Carcinoma, Pancreatic Ductal

Interventions

Type	Name	Description
DRUG	S1	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.
DRUG	Oxaliplatin	Patients are planned to receive the SIRIOX regimen including Oxaliplatin (OXA, 85 mg/m2; d1,d15) of every cycle. • 28 days a cycle
DRUG	Irinotecan	Patients are planned to receive the SIRIOX regimen including Irinotecan (IRI, 180mg/m2; day 1,day 15) of every cycle. • 28 days a cycle

Timeline

• Start date: 2020-07-01
• Primary completion: 2023-12-31
• Completion: 2024-07-01
• First posted: 2018-01-18
• Last updated: 2021-04-09

Locations

2 sites across 1 country: China