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

  • STATUS
    Recruiting
  • End date
    Jul 1, 2024
  • participants needed
    65
  • sponsor
    Fudan University
Updated on 26 February 2022

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 uoropyrimidine 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.

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-uorouracil'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.

Details
Condition Carcinoma, Pancreatic Ductal
Treatment Irinotecan, Oxaliplatin, S1
Clinical Study IdentifierNCT03403101
SponsorFudan University
Last Modified on26 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients aged 18 - 75 years old at the time of signing the ICF
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)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Adequate hematologic function defined as: absolute neutrophil count (ANC) >= 2,000/L; platelets count >= 100,000/L; hemoglobin must be >= 10 g/dL (can be corrected by growth factor or transfusion)
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)
Adequate renal function with: serum creatinine =< 1.3 mg/dL or calculated creatinine clearance >= 60 mL/minute according to the Cockcroft and Gault formula
At least one measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Life expectancy over 12 weeks
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
Willing and able to comply with all aspects of the treatment protocol
Provide written informed consent

Exclusion Criteria

Patients who are unwilling or unable to comply with the study protocol
Existing anticancer treatment-related toxicities of Grades >= 2 (except for alopecia and neuropathy) according to Common Terminology Criteria for Adverse Events (CTCAE v4.03)
Simultaneously using targeted therapies, such as Erlotinib, Nimotuzumab etc
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)
Large operations were performed within 14 days before entering the study, or there were surgical incisions that were not completely healed
Women who are pregnant or breastfeeding
Ascertained hypersensitivity to investigational product, Oxaliplatin, Irinotecan, and S1 or any of the excipients used in the study
History of other malignancies within 5 years, except for adequately treated basal cell carcinoma or squamous cell carcinoma or carcinoma in situ
Obvious gastrointestinal injury history, the researchers estimate may significantly affect the absorption of S1 on the whole, including the ability to swallow drugs
Other combinations of anticancer therapies (including LHRH agonists, anticancer herbs, immunotherapy), except steroid hormones
Patients with UGT1A1 mutations or congenital disease lack of UGT1A1 expression (e.g. Crigler-Najjar syndrome and Gilbert syndrome)
Patients with DPD enzyme deficiency
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
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