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

• Status: Recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fudan University
• Treatments: Camptothecin; Irinotecan; Oxaliplatin

Criteria

Inclusion Criteria:

1. Patients aged 18 - 75 years old at the time of signing the ICF.

2. Patients with pathologically proved adenocarcinoma of pancreatic cancer and diagnosed with inoperable/metastatic disease (previous systemic chemotherapy, neoadjuvant or adjuvant are acceptable without Irinotecan, Oxaliplatin, or S1).

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

4. Adequate hematologic function defined as: absolute neutrophil count (ANC) >= 2,000/μL; platelets count >= 100,000/μL; hemoglobin must be >= 10 g/dL (can be corrected by growth factor or transfusion).

5. Adequate hepatic function defined as: serum bilirubin =< 1.5-fold upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =< 3-fold ULN (5-fold ULN if liver metastasis is observed).

6. Adequate renal function with: serum creatinine =< 1.3 mg/dL or calculated creatinine clearance >= 60 mL/minute according to the Cockcroft and Gault formula.

7. At least one measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

8. Life expectancy over 12 weeks.

9. Women must be either of non-child bearing potential, or women with child-bearing potential agree to use effective a highly contraceptive method or a contraceptive implant, exception of hormonal contraception (estrogen/progesterone), during treatment from time of Screening Visit and after cessation of therapy at least 3 months.

10. Willing and able to comply with all aspects of the treatment protocol.

11. Provide written informed consent.

Exclusion Criteria:

1. Patients who are unwilling or unable to comply with the study protocol;

2. Existing anticancer treatment-related toxicities of Grades >= 2 (except for alopecia and neuropathy) according to Common Terminology Criteria for Adverse Events (CTCAE v4.03).

3. Simultaneously using targeted therapies, such as Erlotinib, Nimotuzumab etc;

4. Any severe or uncontrolled systemic disease (e.g., unstable or decompensated breathing, heart, liver or kidney disease, HIV infection, hypertension, severe arrhythmia, diabetes mellitus, massive active bleeding);

5. Large operations were performed within 14 days before entering the study, or there were surgical incisions that were not completely healed;

6. Women who are pregnant or breastfeeding;

7. Ascertained hypersensitivity to investigational product, Oxaliplatin, Irinotecan, and S1 or any of the excipients used in the study.

8. History of other malignancies within 5 years, except for adequately treated basal cell carcinoma or squamous cell carcinoma or carcinoma in situ;

9. Obvious gastrointestinal injury history, the researchers estimate may significantly affect the absorption of S1 on the whole, including the ability to swallow drugs;

10. Other combinations of anticancer therapies (including LHRH agonists, anticancer herbs, immunotherapy), except steroid hormones;

11. Patients with UGT1A1 mutations or congenital disease lack of UGT1A1 expression (e.g. Crigler-Najjar syndrome and Gilbert syndrome);

12. Patients with DPD enzyme deficiency.

13. Judged to be not applicable to this study by investigator such as difficulty of follow-up observation, psychiatric disorder, with any other serious diseases/medical history.